Treatment of symptoms associated with SARS-cov viral infection or a prior SARS-cov viral infection with nuclease agents

Abstract

The present disclosure provides methods for treating symptoms (e.g., fatigue, reduced cognitive function, inflammation) associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection or prior SARS-CoV viral infection by administering a nuclease agent to a subject.

Description

[0001]RVY-02325 TREATMENT OF SYMPTOMS ASSOCIATED WITH SARS-CoV VIRAL INFECTION OR A PRIOR SARS-CoV VIRAL INFECTION WITH NUCLEASE AGENTS RELATED APPLICATIONS This application claims the benefit of U.S. Patent Application No.63 / 618,266, filed January 5, 2024. The entire contents of which is incorporated herein by reference in its entirety. BACKGROUND OF THE DISCLOSURE Of the estimated 770 million patients worldwide infected with the SARS-CoV-2 virus, approximately 20% experience severe debilitating symptoms that persist for months to years following the acute illness. Patients with long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC) have a complex constellation of symptoms involving major organ systems, including immune system dysregulation, cognitive impairment, fatigue, pulmonary, cardiovascular, endothelial, renal, and gastrointestinal symptoms. Additional symptoms include difficulty with thinking and concentration (e.g., brain fog), inflammation, shortness of breath, cough, joint pain, and chest pain among others. Fatigue, which is characterized in terms of intensity, duration, and effects on daily function may be worsened by mental or physical activity and is not ameliorated with rest. While the symptoms of PASC vary considerably among patients, severe debilitating fatigue is one of the few that is shared by the majority of patients. Thus, there exists a need for a means to improve symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection or a prior SARS-CoV viral infection. SUMMARY The present disclosure provides methods and compositions for treating one or more symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection or a prior SARS-CoV viral infection in a subject. The present disclosure further provides nuclease agents (for example, RNase-containing nuclease fusion proteins and, for example, RNase-Fc fusion proteins) for digesting circulating viral RNA (and RNA associated with autoantibodies) and removing it from circulation and thereby decreasing symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) viral infection. RVY-02325 In some embodiments, symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection include, for example, fatigue, inflammation, cognitive impairment, reduced cognitive function, brain fog, depression, concentration difficulties, and hypercytokinemia (i.e., cytokine storm)). In some aspects, the disclosure provides a method for treating one or more symptoms associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, the method comprising administering an effective amount of a composition comprising a nuclease agent to the subject, thereby treating the one or more symptoms in the subject. In some embodiments of any of the foregoing or related aspects, SARS-CoV is SARS- CoV-2. In some embodiments, SARS-CoV is SARS-CoV-1. In some embodiments of any of the foregoing or related aspects, the infection is an acute infection. In some embodiments, the infection is a prior infection. In some embodiments of any of the foregoing or related aspects, the symptom is fatigue. In some embodiments, the symptom is inflammation. In some embodiments of any of the foregoing or related aspects, the symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC). In some embodiments of any of the foregoing or related aspects, treatment reduces serum ferritin levels. In some embodiments of any of the foregoing or related aspects, treatment reduces serum c-reactive protein (CRP) levels in the subject. In some embodiments of any of the foregoing or related aspects, treatment reduces anti- phospholipid IgG in the subject. In some aspects, the disclosure provides a method for treating fatigue associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, the method comprising administering an a first dose of a composition comprising a nuclease agent to the subject and at least one subsequent dose to the subject, and wherein the nuclease agent is administered to the subject at an amount of about 5-10 mg / kg, thereby treating fatigue in the subject. RVY-02325 In some embodiments of any of the foregoing or related aspects, treatment reduces fatigue in the subject according to the Patient Reported Outcome Measurement Information System (PROMIS) SF 7a. In some embodiments of any of the foregoing or related aspects, treatment reduces fatigue in the subject by a minimal clinically important improvement (MCII) in a PROMIS score. In some embodiments of any of the foregoing or related aspects, treatment reduces fatigue in the subject by at least 0.5 standard deviation in the subject as measured by a PROMIS score. In some embodiments, treatment reduces fatigue in the subject by at least 1 standard deviation in the subject as measured by a PROMIS score. In some embodiments, treatment reduces fatigue in the subject by at least 1.5 standard deviation in the subject as measured by a PROMIS score. In some embodiments, treatment reduces fatigue in the subject by at least 10- 15% on the PROMIS score. In some embodiments of any of the foregoing or related aspects, the PROMIS score is evaluated prior to treatment and after at least 2 doses of the nuclease agent have been administered to the subject. In some embodiments, the PROMIS score is evaluated prior to treatment and after at least 3 doses of the nuclease agent have been administered to the subject. In some embodiments, the PROMIS score is evaluated prior to treatment and after at least 4 doses of the nuclease agent have been administered to the subject. In some embodiments of any of the foregoing or related aspects, treatment reduces fatigue in the subject according to the Physicians Global Assessment (PGA). In some embodiments, treatment reduces fatigue in the subject by a minimal clinically important improvement (MCII) on a PGA score. In some embodiments, treatment reduces fatigue in the subject by at least 10-15% on the PGA score. In some embodiments of any of the foregoing or related aspects, the PGA score is evaluated prior to treatment and after at least two doses of the nuclease agent have been administered to the subject. In some embodiments, the PGA score is evaluated prior to treatment and after at least 3 doses of the nuclease agent have been administered to the subject. In some embodiments, the PGA score is evaluated prior to treatment and after at least 4 doses of the nuclease agent have been administered to the subject. RVY-02325 In some embodiments of any of the foregoing or related aspects, treatment reduces fatigue in the subject according to the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale. In some embodiments, treatment reduces fatigue in the subject by a minimal clinically important improvement (MCII) on a Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale. In some embodiments, treatment reduces fatigue in the subject by at least 10-15% on the FACIT fatigue scale. In some embodiments, treatment reduces fatigue in the subject by at least a 6-point improvement on the FACIT fatigue scale. In some embodiments of any of the foregoing or related aspects, the FACIT fatigue score is evaluated prior to treatment and after at least two doses of the nuclease agent have been administered to the subject. In some embodiments, the FACIT fatigue score is evaluated prior to treatment and after at least 3 doses of the nuclease agent have been administered to the subject. In some embodiments, the FACIT fatigue score is evaluated prior to treatment and after at least 4 doses of the nuclease agent have been administered to the subject. In some aspects, the disclosure provides a method for reducing inflammation associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, the method comprising administering a first dose of a composition comprising a nuclease agent to the subject and at least one subsequent dose to the subject, and wherein the nuclease agent is administered to the subject at an amount of about 5-10 mg / kg, thereby reducing inflammation in the subject. In some embodiments of any of the foregoing or related aspects, the method reduces serum ferritin levels. In some embodiments, the method reduces serum ferritin levels by at least 10-15%. In some embodiments, the method reduces serum ferritin levels by at least 10%. In some embodiments, the method reduces serum ferritin levels by at least 15%. In some embodiments of any of the foregoing or related aspects, the method reduces serum c-reactive protein (CRP) levels in the subject. In some embodiments, the method reduces serum c-reactive protein (CRP) levels in the subject by at least 10-15%. In some embodiments, the method reduces serum c-reactive protein (CRP) levels in the subject by at least 10%. In some embodiments, the method reduces serum c-reactive protein (CRP) levels in the subject by at least 15%. In some embodiments of any of the foregoing or related aspects, the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 1 RVY-02325 month to about 2 years prior to treatment. In some embodiments, the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 6 months prior to treatment. In some embodiments, the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 1 month to about 3 months prior to treatment. In some embodiments, the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 3 months to about 6 months prior to treatment. In some embodiments, the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 6 months to about 9 months prior to treatment. In some embodiments, the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 9 months to about 12 months prior to treatment. In some embodiments, the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 6 months to about 12 months prior to treatment. In some embodiments, the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 1 year to about 3 years prior to treatment. In some embodiments of any of the foregoing or related aspects, the subject is a human subject. In some embodiments, the subject is a female subject. In some embodiments of any of the foregoing or related aspects, the subject is positive for anti-nuclear antibodies (ANA). In some embodiments, the subject is positive for anti-nuclear antibodies (ANA) prior to treatment. In some embodiments of any of the foregoing or related aspects, the nuclease agent is administered at a dose of about 10mg / kg. In some embodiments of any of the foregoing or related aspects, the nuclease agent is administered to the subject via intravenous administration. In some embodiments, the nuclease agent is administered to the subject via subcutaneous administration. In some embodiments of any of the foregoing or related aspects, at least 2 doses of the nuclease agent are administered to the subject. In some embodiments, at least 3 doses of the nuclease agent are administered to the subject. In some embodiments, at least 4 doses of the nuclease agent are administered to the subject. In some embodiments, at least 5 doses of the nuclease agent are administered to the subject. In some embodiments, at least 6 doses of the nuclease agent are administered to the subject. RVY-02325 In some embodiments of any of the foregoing or related aspects, the nuclease agent is administered to the subject once weekly. In some embodiments, the nuclease agent is administered to the subject once monthly. In some embodiments, the nuclease agent is administered to the subject every two weeks. In some embodiments, the nuclease agent is administered to the subject twice monthly. In some embodiments of any of the foregoing or related aspects, at least 2 doses of the nuclease agent are administered to the subject once weekly. In some embodiments, at least 3 doses of the nuclease agent are administered to the subject once weekly. In some embodiments, at least 4 doses of the nuclease agent are administered to the subject once weekly. In some embodiments, at least 5 doses of the nuclease agent are administered to the subject once weekly. In some embodiments, at least 6 doses of the nuclease agent are administered to the subject once weekly. In some embodiments, the nuclease agent is administered to the subject to achieve or maintain a therapeutic effect. In some embodiments of any of the foregoing or related aspects, the nuclease agent is administered to the subject once weekly to achieve or maintain a therapeutic effect. In some embodiments, the nuclease agent is administered to the subject once monthly to achieve or maintain a therapeutic effect. In some embodiments, the nuclease agent is administered to the subject twice monthly to achieve or maintain a therapeutic effect. In some embodiments, the nuclease agent is administered to the patient every week for two weeks, and then one administration every two weeks to achieve or maintain a therapeutic effect. In some embodiments, the nuclease agent is administered to the patient every week for three weeks, and then one administration every two weeks to achieve or maintain a therapeutic effect. In some embodiments of any of the foregoing or related aspects, the subject experienced moderate or severe fatigue at screening as determined by PROMIS SF 7a. In some embodiments, the subject experienced fatigue at least 0.5 standard deviations above normal at screening as determined by PROMIS SF 7a. In some embodiments, the subject experienced fatigue at least 1 standard deviations above normal at screening as determined by PROMIS SF 7a. In some embodiments, the subject experienced fatigue at least 1.5 standard deviations above normal at screening as determined by PROMIS SF 7a. In some embodiments, the subject experienced moderate or severe fatigue at screening as determined PGA. In some embodiments, the subject experienced fatigue at least 1-15% above normal at screening as determined PGA. RVY-02325 In some embodiments of any of the foregoing or related aspects, the subject experienced moderate or severe fatigue at screening as determined by a FACIT fatigue scale. In some embodiments, the subject had a FACIT-fatigue score of less than 20-40 at screening as determined by a FACIT fatigue scale. In some embodiments, the subject had a FACIT-fatigue score of less than 40 at screening as determined by a FACIT fatigue scale. In some embodiments, the subject had a FACIT-fatigue score of less than 35 at screening as determined by a FACIT fatigue scale. In some embodiments, the subject had a FACIT-fatigue score of less than 30 at screening as determined by a FACIT fatigue scale. In some embodiments, the subject had a FACIT-fatigue score of less than 25 at screening as determined by a FACIT fatigue scale. In some embodiments, the subject had a FACIT-fatigue score of less than 20 at screening as determined by a FACIT fatigue scale. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises an RNase domain and an Fc domain. In some embodiments of any of the foregoing or related aspects, the RNase domain comprises a human pancreatic RNase 1. In some embodiments, the human pancreatic RNase 1 comprises the amino acid sequence as set forth in SEQ ID NO: 2. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises a wild-type human IgG1 Fc domain or a human IgG1 Fc domain comprising one or more mutations. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises an RNase domain operably linked, with or without a linker domain, to an Fc domain. In some embodiments, the RNase domain is operably linked, with or without a linker domain, to the N-terminus of the Fc domain. In some embodiments, the RNase domain is operably linked, with or without a linker domain, to the C-terminus of the Fc domain. In some embodiments of any of the foregoing or related aspects, the nuclease agent further comprises a DNase domain. In some embodiments, the DNase domain is a mutant human DNase domain. In some embodiments, the mutant human DNase domain comprises a G105R mutation and an A114F mutation. In some embodiments of any of the foregoing or related aspects, the mutant human DNase domain comprises the amino acid sequence set forth as SEQ ID NO: 29, or a nuclease RVY-02325 agent comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 29. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises an RNase domain operably linked, with or without a linker domain, to the N- or C- terminus of an Fc domain and a DNase domain operably linked, with or without a linker domain, to the N- or C- terminus of the Fc domain. In some embodiments of any of the foregoing or related aspects, the Fc domain comprising one or more mutations has decreased binding to Fc^ receptors on human cells. In some embodiments of any of the foregoing or related aspects, the nuclease agent has a reduced effector function optionally selected from the group consisting of opsonization, phagocytosis, complement dependent cytotoxicity, and antibody-dependent cellular cytotoxicity. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises a human IgG1 Fc domain comprising a P238S mutation and a P331S mutation according to EU numbering. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises a human IgG1 Fc domain comprising a hinge domain, a CH2 domain and a CH3 domain. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises a human IgG1 Fc domain comprising a substitution of one or more of three hinge region cysteine residues with serine. In some embodiments, the nuclease agent comprises an Fc domain comprising an SCC mutation (residues 220, 226, and 229), numbering according to the EU index. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises a human IgG1 Fc domain comprising the amino acid sequence as set forth in SEQ ID NO: 22. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises an amino acid sequence as set forth in SEQ ID NO: 50, or a nuclease agent comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 50. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises an amino acid sequence as set forth in SEQ ID NO: 50. In some embodiments of RVY-02325 any of the foregoing or related aspects, the nuclease agent comprises an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 50. In some embodiments of any of the foregoing or related aspects, the nuclease agent is a dimeric nuclease agent. In some embodiments, the dimeric nuclease agent is a homodimer. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises a first nuclease domain, a second nuclease domain, and an Fc domain, wherein the first nuclease domain is DNase1 and the second nuclease domain is RNase1, wherein the DNase1 is operably linked with or without a linker in tandem from N- to C- terminus to the RNase1, and the Rnase1 is operably linked with or without a linker to the Fc domain. In some embodiments of any of the foregoing or related aspects, the RNase 1 is operably linked to the N-terminus of the Fc domain without a linker. In some embodiments, the RNase 1 is operably linked to the C-terminus of the Fc domain without a linker. In some embodiments of any of the foregoing or related aspects, the DNase 1 is operably linked to the RNase 1 via a linker. In some embodiments of any of the foregoing or related aspects, the RNase is a wild type human RNase 1, or a mutant RNase, such as an aglycosylated, underglycosylated, or deglycosylated RNase 1, such as human RNase 1 N34S / N76S / N88S. In some embodiments of any of the foregoing or related aspects, the RNase is wild type human RNase 1. In some embodiments of any of the foregoing or related aspects, the DNase is a wild type human DNase 1, or a mutant human DNase 1 A114F, or aglycosylated, underglycosylated, or deglycosylated mutant human DNase1 N18S / N106S / A114F. In some embodiments of any of the foregoing or related aspects, the Fc domain comprises a hinge domain, a CH2 domain, and a CH3 domain. In some embodiments of any of the foregoing or related aspects, the Fc domain comprises a substitution in one or more of three hinge region cysteine residues with serine. In some embodiments, the Fc domain comprises a mutation selected from the group consisting of SCC, SSS (residues 220, 226, and 229), G236R, L328R, L234A, and L235A, numbering according to the EU index. In some embodiments, the Fc domain comprises an SCC mutation (residues 220, 226, and 229), numbering according to the EU index. In some embodiments, the Fc domain comprises a P238S and a P331S mutation, numbering according to the EU index. RVY-02325 In some embodiments of any of the foregoing or related aspects, the linker domain is a polypeptide linker, such as a gly-ser linker or an NLG linker (vdgasspvnvsspsvqdi). In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises an amino acid sequence set forth in SEQ ID NO: 59 or SEQ ID NO: 60, or a nuclease agent comprising an amino acid se sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 59 or SEQ ID NO: 60. In some embodiments of any of the foregoing or related aspects, the nuclease agent is a dimeric nuclease agent. In some embodiments, the dimeric nuclease agent is a homodimer. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises a heterodimer comprising a first nuclease domain, a second nuclease domain, a first Fc domain and a second Fc domain, wherein the first nuclease domain is DNasel and the second nuclease domain is RNasel, wherein the DNasel is operably linked with or without a linker to the N- or C- terminus of the first Fc domain, and the RNasel is operably linked with or without a linker to the N- or C- terminus of the second Fc domain. In some embodiments of any of the foregoing or related aspects, the DNase 1 is operably linked without a linker to the N-terminus of the first Fc domain and the RNase l is operably linked without a linker to the N-terminus of the second Fc domain. In some embodiments of any of the foregoing or related aspects, the DNase 1 is operably linked with a linker to the N-terminus of the first Fc domain and the RNase l is operably linked with a linker to the N-terminus of the second Fc domain. In some embodiments of any of the foregoing or related aspects, the DNase 1 is operably linked with a linker to the N-terminus of the first Fc domain and the RNase l is operably linked without a linker to the C -terminus of the second Fc domain. In some embodiments of any of the foregoing or related aspects, the DNase 1 is operably linked without a linker to the N-terminus of the first Fc domain and the Rnase l is operably linked without a linker to the C-terminus of the second Fc domain. In some embodiments of any of the foregoing or related aspects, the DNase 1 is operably linked with a linker to the N-terminus of the first Fc domain and the RNase l is operably linked with a linker to the C-terminus of the second Fc domain. RVY-02325 In some embodiments of any of the foregoing or related aspects, the DNase 1 is operably linked with a linker to the C- terminus of the first Fc domain and the RNase l is operably linked with a linker to the C-terminus of the second Fc domain. In some embodiments of any of the foregoing or related aspects, the DNase 1 is operably linked without a linker to the C- terminus of the first Fc domain and the RNase l is operably linked without a linker to the C-terminus of the second Fc domain. In some embodiments of any of the foregoing or related aspects, the DNase 1 is operably linked with a linker to the C- terminus of the first Fc domain and the RNase l is operably linked without a linker to the N-terminus of the second Fc domain. In some embodiments of any of the foregoing or related aspects, the DNase 1 is operably linked with a linker to the C- terminus of the first Fc domain and the RNase l is operably linked with a linker to the N-terminus of the second Fc domain. In some embodiments of any of the foregoing or related aspects, the RNase is a wild type human RNase l, or a mutant RNase, such as an aglycosylated, underglycosylated, or deglycosylated RNase 1, such as human RNase l N34S / N76S / N88S. In some embodiments of any of the foregoing or related aspects, the RNase is wild type human RNase l. In some embodiments of any of the foregoing or related aspects, the DNase is a wild type human DNase l, or a mutant human DNase l A114F, or an aglycosylated, underglycosylated, or deglycosylated mutant human DNase l N18S / N106S / A114F. In some embodiments of any of the foregoing or related aspects, the first and second Fc domains comprise a hinge domain, a CH2 domain and a CH3 domain. In some embodiments of any of the foregoing or related aspects, the first and second Fc domains comprise a substitution of one or more of three hinge region cysteine residues with serine. In some embodiments, the first and second Fc domains comprise a mutation selected from the group consisting of SCC, SSS (residues 220, 226, and 229), G236R, L328R, L234A, and L235A, numbering according to the EU index. In some embodiments, the first and second Fc domains comprise an SCC mutation (residues 220, 226, and 229), numbering according to the EU index. In some embodiments, the first and second Fc domains comprise a P238S and a P331 mutation, numbering according to the EU index. RVY-02325 In some embodiments of any of the foregoing or related aspects, the first and second Fc domains comprise one or more CH3 mutations to preferentially form heterodimers. In some embodiments of any of the foregoing or related aspects, the first Fc domain comprises CH3 mutations T350V, L351Y, F405A, and Y407V, and the second Fc domain comprises CH3 mutations T350V, T366L, K392L, T394W, numbering according to the EU index. In some embodiments of any of the foregoing or related aspects, the linker domain is a polypeptide linker, such as a gly-ser linker or an NLG linker (vdgasspvnvsspsvqdi). In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises a heterodimer comprising a first and second polypeptide sequence selected from the group consisting of: (i) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 61, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:61; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 62, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 62, or (ii) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 65, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:65; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 66, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:66, or (iii) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO:67, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 67; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 68, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 68, or (iv) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 69, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 69; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 70, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 70, or RVY-02325 (v) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 73, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 73; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 74, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 74. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises a heterodimer comprising a first nuclease domain, a second nuclease domain and a first Fc domain and a second Fc domain, wherein the first nuclease domain is DNase l and the second nuclease domain is RNase l, wherein (i) the DNase l is operably linked with or without a linker to the N-terminus of the first Fc domain, and the RNase l is operably linked with or without a linker to the C- terminus of the first Fc domain, or (ii) the RNase l is operably linked with or without a linker to the N-terminus of the first Fc domain, and the DNase l is operably linked with or without a linker to the C- terminus of the first Fc domain. In some embodiments of any of the foregoing or related aspects, the DNase 1 is operably linked without a linker to the N-terminus of the first Fc domain and the RNase l is operably linked with a linker to the C-terminus of the first Fc domain. In some embodiments of any of the foregoing or related aspects, the DNase 1 is operably linked with a linker to the N-terminus of the first Fc domain and the RNase l is operably linked with a without a linker to the C-terminus of the first Fc domain. In some embodiments of any of the foregoing or related aspects, the RNase 1 is operably linked without a linker to the N-terminus of the first Fc domain and the DNase 1 is operably linked with a linker to the C-terminus of the first Fc domain. In some embodiments of any of the foregoing or related aspects, the RNase 1 is operably linked with a linker to the N-terminus of the first Fc domain and the DNase 1 is operably linked with a linker to the C-terminus of the first Fc domain. In some embodiments of any of the foregoing or related aspects, the RNase is a wild type human RNase l, or a mutant RNase, such as an aglycosylated, underglycosylated, or deglycosylated RNase 1, such as human RNase l N34S / N76S / N88S. RVY-02325 In some embodiments of any of the foregoing or related aspects, the RNase is wild type human RNase l. In some embodiments of any of the foregoing or related aspects, the DNase is a wild type human DNase l, or a mutant human DNase l A114F, or an aglycosylated, underglycosylated, or deglycosylated mutant human DNase l N18S / N106S / A114F. In some embodiments of any of the foregoing or related aspects, the first and second Fc domains comprise a hinge domain, a CH2 domain and a CH3 domain. In some embodiments of any of the foregoing or related aspects, the first and second Fc domains comprise a substitution of one or more of three hinge region cysteine residues with serine. In some embodiments, the first and second Fc domains comprise a mutation selected from the group consisting of SCC, SSS (residues 220, 226, and 229), G236R, L328R, L234A, and L235A, numbering according to the EU index. In some embodiments, the first and second Fc domains comprise an SCC mutation (residues 220, 226, and 229), numbering according to the EU index. In some embodiments, the first and second Fc domains comprise a P238S and a P331 mutation, numbering according to the EU index. In some embodiments of any of the foregoing or related aspects, the first and second Fc domains comprise one or more CH3 mutations to preferentially form heterodimers. In some embodiments of any of the foregoing or related aspects, the first Fc domain comprises CH3 mutations T350V, L351Y, F405A, and Y407V, and the second Fc domain comprises CH3 mutations T350V, T366L, K392L, T394W, numbering according to the EU index. In some embodiments of any of the foregoing or related aspects, the linker domain is a polypeptide linker, such as a gly-ser linker or an NLG linker (vdgasspvnvsspsvqdi). In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises a heterodimer comprising a first and second polypeptide sequence selected from the group consisting of: (i) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO:63, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:63; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO:64, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:64, or RVY-02325 (ii) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 71, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 71; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 72, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 72. In some aspects, the disclosure provides a kit comprising a container comprising an injectable solution and instructions for use in treating one or more symptoms associated with SARS-CoV viral infection or prior SARS-CoV viral infection in a human subject in need thereof, comprising: a composition comprising an effective amount of a nuclease agent; and one or more pharmaceutically acceptable carriers and / or diluents. In some embodiments of any of the foregoing or related aspects, the nuclease agent comprises an amino acid sequence as set forth in SEQ ID NO: 50. In some embodiments of any of the foregoing or related aspects, the nuclease agent is a dimeric nuclease agent. In some embodiments, the dimeric nuclease agent is a homodimer. In some embodiments of any of the foregoing or related aspects, the composition comprising the nuclease agent is formulated to be administered at a dose of about 5-10mg / kg. In some embodiments of any of the foregoing or related aspects, the injectable solution is formulated to be administered via intravenous administration. In some embodiments, the injectable solution is formulated to be administered via subcutaneous administration. In some aspects, the disclosure provides a nuclease agent for use in treating one or more symptoms associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof. In some aspects, the disclosure provides a nuclease agent for use in treating fatigue associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, wherein the nuclease agent is formulated as a composition to be administrable as a first dose and at least one subsequent dose to the subject, and wherein the nuclease agent is formulated to be administrable at an amount of about 5-10 mg / kg. In some aspects, the disclosure provides a nuclease agent for use in reducing inflammation associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, wherein the nuclease agent is formulated as a composition to be RVY-02325 administrable as a first dose and at least one subsequent dose to the subject, and wherein the nuclease agent is formulated to be administrable at an amount of about 5-10 mg / kg. In some aspects, the disclosure provides for use of a nuclease agent in the manufacture of a medicament for treating one or more symptoms associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof. In some aspects, the disclosure provides for use of a nuclease agent in the manufacture of a medicament for treating fatigue associated with a SARS-CoV virus infection or prior SARS- CoV virus infection in a human subject in need thereof, wherein the nuclease agent is formulated as a composition to be administrable as a first dose and at least one subsequent dose to the subject, and wherein the nuclease agent is formulated to be administrable at an amount of about 5-10 mg / kg. In some aspects, the disclosure provides for use of a nuclease agent in the manufacture of a medicament for reducing inflammation associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, wherein the nuclease agent is formulated as a composition to be administrable as a first dose and at least one subsequent dose to the subject, and wherein the nuclease agent is formulated to be administrable at an amount of about 5-10 mg / kg. In some embodiments of any of the foregoing or related aspects, treatment results in an increase or decrease in expression of one or more genes in response to one or more interferon proteins. In some embodiments, the one or more interferon proteins are alpha interferon proteins. In some embodiments, the interferon protein is IFN^. In some embodiments, the one or more interferon proteins are gamma interferon proteins. In some embodiments, the interferon protein is IFN^. In some embodiments of any of the foregoing or related aspects, the subject is female, and treatment results in an increase or decrease in expression of one or more genes in response to one or more interferon proteins. In some embodiments, the one or more interferon proteins are alpha interferon proteins. In some embodiments, the interferon protein is IFN^. In some embodiments, the one or more interferon proteins are gamma interferon proteins. In some embodiments, the interferon protein is IFN^. RVY-02325 In some embodiments of any of the foregoing or related aspects, the subject is female and treatment results in a decrease in expression of at least one gene of a Hallmark Interferon Alpha Response gene set relative to expression of the at least one gene in the subject prior to treatment. In some embodiments of any of the foregoing or related aspects, the subject is female and treatment results in a decrease in expression of at least one gene selected from NUB1, PARP12, OASL, MOV10, MX1, TRIM14, UBA7, IFI44, DDX60, PSMB8, USP18, BATF2, IFIH1, GBP4, PSME2, C1S, SLC25A28, NCOA7, RSAD2, CMPK2, LY6E, CSF1, LPAR6, IFI44L, EPSTI1, CXCL10, PSME1, OAS1, LAMP3, TRIM26, LAP3, CD74, CNP, or any combination thereof relative to expression of the at least one genes in the female subject prior to treatment. In some embodiments of any of the foregoing or related aspects, the subject is female and treatment results in a decrease in expression of at least one gene of a Hallmark Interferon Gamma Response gene set relative to expression of the at least one gene in the female subject prior to treatment. In some embodiments of any of the foregoing or related aspects, the subject is female and treatment results in a decrease in expression of at least one gene selected from IFI35, PML, CFB, STAT4, CD86, VAMP5, LCP2, PARP12, OASL, HLA-B, CXCL9, GPR18, APOL6, VAMP8, ISOC1, PFKP, VCAM1, MX1, TRIM14, NCOA3, RAPGEF6, IFI44, DDX60, CMKLR1, BANK1, GCH1, PSMB8, USP18, NFKB1, BATF2, IFIH1, IFIT1, SLAMF7, HLA-A, OAS2, GBP4, IL2RB, PSME2, SERPING1, C1S, CIITA, CD69, SLC25A28, RSAD2, PTPN1, PTGS2, CMPK2, PSMB10, LY6E, NUP93, C1R, IL6, IFI44L, CFH, EPSTI1, IRF8, CXCL10, IDO1, HLA-DMA, PSME1, ARID5B, MTHFD2, ITGB7, IRF5, SAMHD1, TRIM26, OAS3, SOCS3, IL18BP, LAP3, CD74, HLA-DRB1, PSMB2, IRF4, IL10RA, HLA-DQA1, and ST3GAL5, relative to expression of the at least one gene in the female subject prior to treatment. BRIEF DESCRIPTION OF THE DRAWINGS FIG.1A depicts the configuration of RSLV-132, a homodimeric nuclease-Fc fusion protein comprising two polypeptides. Each polypeptide of the homodimer has the configuration RNase- Fc, wherein a wild-type human RNase 1 domain is operably coupled without a linker to the N- terminus of a human IgG1 Fc domain comprising an SCC hinge and CH2 mutations P238S and P331S. RVY-02325 FIG.1B depicts the configuration of RSLV-133, a homodimeric binuclease-Fc fusion protein. Each polypeptide of the homodimer has the configuration RNase-Fc-DNase, wherein a wild-type human RNase 1 domain is operably coupled without a linker to the N-terminus of a human IgG1 Fc domain comprising SCC hinge and CH2 mutations P238S and P331S and a mutant human DNase domain comprising mutations G105R and A114F is operably coupled via an NLG linker to the C-terminus of the human IgG1 Fc domain. FIG.1C depicts the configuration of RSLV-145, a tandem homodimeric binuclease-Fc fusion protein. Each polypeptide of the homodimer has the configuration DNase-linker-RNase-Fc, wherein a wild-type, human RNase 1 domain is operably coupled without a linker to the N- terminus to a mutant Fc region comprising SCC hinge and CH2 mutations P238S, P331S and a mutant human DNase 1 domain is operably coupled to the N-terminus of the RNase 1 domain via a NLG linker. FIG.1D depicts exemplary heterodimeric binuclease-Fc fusion proteins. FIG.2 depicts a flow chart of the study participant disposition. Eligible subjects were randomized 2:1 (RSLV-132:placebo) to receive a total of 6 intravenous infusions over 57 days of placebo or 10 mg / kg RSLV-132 at baseline then weekly for 3 weeks followed by two bi-weekly infusions over one month. FIG.3 depicts the overall change from baseline in mean PROMIS score for the RSLV-132 and placebo groups (N=95). The change from baseline in mean PROMIS fatigue scores are shown for the indicated study day. FIG.4 depicts the change from baseline in PROMIS score for the female participants (N=48). The change from baseline in mean PROMIS fatigue scores are shown for the indicated study day. FIG.5 depicts the change from baseline in PROMIS score for the male participants (N=47). The change from baseline in mean PROMIS fatigue scores are shown for the indicated study day. FIG.6 depicts the overall change from baseline in mean PGA score for the RSLV-132 and placebo groups (N=95). The change from baseline in mean PGA scores are shown for the indicated study day. FIG.7 depicts the change from baseline in PGA score for the female participants (N=48). The change from baseline in mean PGA scores are shown for the indicated study day. RVY-02325 FIG.8 depicts the change from baseline in PGA score for the male participants (N=47). The change from baseline in mean PGA scores are shown for the indicated study day. FIG.9 depicts the overall change from baseline in mean FACIT fatigue scores for the RSLV- 132 and placebo groups. FIG.10 depicts the change from baseline in FACIT fatigue scores for female subjects treated with placebo or RSLV-132. FIG.11 depicts the change from baseline in FACIT fatigue scores for male subjects treated with placebo or RSLV-132. FIG.12 depicts the change from baseline in PROMIS score for the ANA-positive participants (N=70). The change from baseline in mean PROMIS fatigue scores are shown for the indicated study day. FIG.13 depicts the change from baseline in PGA score for the ANA-positive participants (N=70). The change from baseline in mean PGA scores are shown for the indicated study day. FIG.14 depicts change from baseline in FACIT fatigue scores for ANA-positive subjects treated with placebo or RSLV-132. FIG.15 depicts the mean change from baseline in serum ferritin levels for the RSLV-132 and placebo groups at day 29 and day 71. FIG.16 depicts the mean change from baseline in serum C-reactive protein (CRP) levels for the RSLV-132 and placebo groups at day 71. FIG.17 depicts the change from baseline in PROMIS scores for female subjects diagnosed with a SARS-CoV (e.g. SARS-CoV-1 and / or SARS-CoV-2) viral infection at least 168 days from baseline but not more than 365 days from baseline and treated with placebo or RSLV-132. FIG.18 depicts the change from baseline in PROMIS scores for male subjects diagnosed with a SARS-CoV (e.g. SARS-CoV-1 and / or SARS-CoV-2) viral infection at least 168 days from baseline but not more than 365 days from baseline and treated with placebo or RSLV-132. FIG.19 depicts the change from baseline in FACIT-F scores for female subjects diagnosed with a SARS-CoV (e.g. SARS-CoV-1 and / or SARS-CoV-2) viral infection at least 168 days from baseline but not more than 365 days from baseline and treated with placebo or RSLV-132. FIG.20 depicts the change from baseline in FACIT-F scores for male subjects diagnosed with a SARS-CoV (e.g. SARS-CoV-1 and / or SARS-CoV-2) viral infection at least 168 days from baseline but not more than 365 days from baseline and treated with placebo or RSLV-132. RVY-02325 FIG.21 depicts the change from baseline in PGA scores for female subjects diagnosed with a SARS-CoV (e.g. SARS-CoV-1 and / or SARS-CoV-2) viral infection at least 168 days from baseline but not more than 365 days from baseline and treated with placebo or RSLV-132. FIG.22 depicts the change from baseline in PGA scores for male subjects diagnosed with a SARS-CoV (e.g. SARS-CoV-1 and / or SARS-CoV-2) viral infection at least 168 days from baseline but not more than 365 days from baseline and treated with placebo or RSLV-132. FIG.23 depicts a heatmap of changes in hallmark gene expression profiles of non-responders and responders to treatment with RSLV-132 at day 71 relative to baseline. FIG.24 depicts a heatmap of changes in hallmark gene expression profiles at day 71 relative to baseline for placebo and RSLV-132 treated subject stratified by male and female. DETAILED DESCRIPTION OF THE DISCLOSURE SARS-CoV-2 RNA and RNA debris can persist in subjects for many months following infection. Although not detectable by typical diagnostic methods, viral RNA has been found in reservoirs within the body for long periods following initial diagnosis. Without being bound by theory, it is believed that these reservoirs of viral RNA may drive the chronic systemic and neuroinflammation responsible for some of the symptoms of PASC. Cells of the human immune system contain RNA sensors, such as TLR7 which detect extremely small amounts of RNA, critical for viral defense. Once activated, they initiate a robust series of inflammatory cascades in an attempt to eliminate RNA from the body. Autoimmune diseases such as SLE and Sjogren’s are thought to be driven by extracellular RNA, either free in circulation of bound to autoantibodies. Since TLR7 is encoded by a locus on the X chromosome, in the event of a failure of X inactivation during development, women get an increased dosage of TLR7 and increased sensitivity to RNA which may account for their increased propensity for autoimmune diseases. Therefore, without being bound by theory, it is believed that the viral RNA and RNA debris play a larger role in women with PASC. The present disclosure is based, at least in part, on the discovery that a therapeutic target in PASC is the viral RNA itself and RNA debris associated with persistent nucleic acid reservoirs. The present Examples demonstrate that digesting the extracellular RNA associated with viral reservoirs in PASC improve fatigue in patient s suffering from PASC. RVY-02325 The present disclosure provides methods and compositions for treating symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection in a subject. RNA viruses (for example, SARS-CoV-1 and / or SARS-CoV-2) release large amounts of RNA into circulation, which triggers an immune response, and in some patients, the development of autoantibodies. Without being bound by theory, it is believed that circulating viral RNA induces symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection, for example, fatigue, inflammation, cognitive impairment, reduced cognitive function, brain fog, depression, concentration difficulties, and hypercytokinemia (i.e., cytokine storm)). Thus, the present disclosure provides nuclease agents (for example, RNase-containing nuclease fusion proteins and, for example, RNase-Fc fusion proteins) for digesting circulating viral RNA (and RNA associated with autoantibodies) and removing it from circulation and thereby decreasing symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. The present disclosure also provides effective treatment and dosing regimens for administering nuclease agents , to human patients with symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection, including patients with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection, in need thereof. The present disclosure also provides compositions comprising a nuclease agent and one or more pharmaceutically acceptable carriers and / or diluents that are useful in methods of treating symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection, methods of reducing fatigue associated a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection, methods of improving cognitive ability patients with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection, and methods of reducing inflammation associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiment, an RNA nuclease agent is RSLV-132. In some embodiments, an RNase-containing nuclease fusion protein is RSLV-132. In some embodiments, an RNase-Fc fusion protein is RSLV-132. RSLV-132 is a biologic drug comprised of a full-length, catalytically active, human RNase moiety fused to the amino terminus of an engineered human IgG1 domain. The drug is engineered to remain in circulation and not enter cells bearing Fc receptors. The RNase portion of RSLV-132 maintained full enzymatic activity compared to wild-type human RNase and has a serum half-life of approximately 19 days. RVY-02325 In some embodiments, an RNA nuclease agent (for example, an RNase-Fc fusion protein) is administered to human patients at a dose of about 5-10 mg / kg, about 8-12 mg / kg, about 2-8 mg / kg, about 3-6 mg / kg, about 3 mg / kg, about 5 mg / kg, about 10 mg / kg, about 12 mg / kg, or about 15 mg / kg. Definitions Terms used in the claims and specification are defined as set forth below unless otherwise specified. "Amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, ^-carboxyglutamate, and O- phosphoserine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an a carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refer to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that function in a manner similar to a naturally occurring amino acid. Amino acids can be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, can be referred to by their commonly accepted single-letter codes. An "amino acid substitution" refers to the replacement of at least one existing amino acid residue in a predetermined amino acid sequence (an amino acid sequence of a starting polypeptide) with a second, different "replacement" amino acid residue. An "amino acid insertion" refers to the incorporation of at least one additional amino acid into a predetermined amino acid sequence. While the insertion will usually consist of the insertion of one or two amino acid residues, larger "peptide insertions" can be made, e.g. insertion of about three to about five or even up to about ten, fifteen, or twenty amino acid residues. The inserted residue(s) RVY-02325 may be naturally occurring or non-naturally occurring as disclosed above. An "amino acid deletion" refers to the removal of at least one amino acid residue from a predetermined amino acid sequence. "Polypeptide," "peptide," and "protein" are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymer. "Nucleic acid" refers to deoxyribonucleotides or ribonucleotides and polymers thereof in either single- or double-stranded form. Unless specifically limited, the term encompasses nucleic acids containing known analogues of natural nucleotides that have similar binding properties as the reference nucleic acid and are metabolized in a manner similar to naturally occurring nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions) and complementary sequences, as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions can be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and / or deoxyinosine residues (Batzer et al., Nucleic Acid Res 1991;19:5081; Ohtsuka et al., JBC 1985;260:2605-8); Rossolini et al., ^^l Cell Probes 1994;8:91-8). For arginine and leucine, modifications at the second base can also be conservative. The term nucleic acid is used interchangeably with gene, cDNA, and mRNA encoded by a gene. Polynucleotides of the present invention can be composed of any polyribonucleotide or polydeoxribonucleotide, which can be unmodified RNA or DNA or modified RNA or DNA. For example, polynucleotides can be composed of single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that can be single-stranded or, more typically, double-stranded or a mixture of single- and double-stranded regions. In addition, the polynucleotide can be composed of triple-stranded regions comprising RNA or DNA or both RNA and DNA. A polynucleotide can also contain one or more modified bases or DNA or RNA backbones modified for stability or for other reasons. "Modified" bases include, for example, tritylated bases and unusual bases such as RVY-02325 inosine. A variety of modifications can be made to DNA and RNA; thus, "polynucleotide" embraces chemically, enzymatically, or metabolically modified forms. As used herein, the term “operably linked” or “operably coupled” refers to a juxtaposition wherein the components described are in a relationship permitting them to function in their intended manner. As used herein, the term “glycosylation” or “glycosylated” refers to a process or result of adding sugar moieties to a molecule. As used herein, the term “altered glycosylation” refers to a molecule that is aglycosylated, deglycosylated, or underglycosylated. As used herein, “glycosylation site(s)” refers to both sites that potentially could accept a carbohydrate moiety, as well as sites within the protein on which a carbohydrate moiety has actually been attached and includes any amino acid sequence that could act as an acceptor for an oligosaccharide and / or carbohydrate. As used herein, the term “aglycosylation” or “aglycosylated” refers to the production of a molecule in an unglycosylated form (e.g., by engineering a protein or polypeptide to lack amino acid residues that serve as acceptors of glycosylation). Alternatively, the protein or polypeptide can be expressed in, e.g., E. coli, to produce an aglycosylated protein or polypeptide. As used herein, the term “deglycosylation” or “deglycosylated” refers to the process or result of enzymatic removal of sugar moieties on a molecule. As used herein, the term “underglycosylation” or “underglycosylated” refers to a molecule in which one or more carbohydrate structures that would normally be present if produced in a mammalian cell has been omitted, removed, modified, or masked. As used herein, the term “fragment crystallizable” or "Fc region" and "Fc domain" is the portion of a native immunoglobulin formed by the respective Fc domains (or Fc moieties) of its two heavy chains without the variable regions which bind antigen. In some embodiments, an Fc domain begins in the hinge region just upstream of the papain cleavage site and ending at the C- terminus of the antibody. Accordingly, a complete Fc domain comprises at least a hinge domain, a CH2 domain, and a CH3 domain. In some embodiments, an Fc domain comprises at least one of: a hinge (e.g., upper, middle, and / or lower hinge region) domain, a CH2 domain, a CH3 domain, a CH4 domain, or a variant, portion, or fragment thereof. In other embodiments, an Fc domain comprises a complete Fc domain (i.e., a hinge domain, a CH2 domain, and a CH3 RVY-02325 domain). In one embodiment, an Fc domain comprises a hinge domain (or portion thereof) fused to a CH3 domain (or portion thereof). In another embodiment, an Fc domain comprises a CH2 domain (or portion thereof) fused to a CH3 domain (or portion thereof). In another embodiment, an Fc domain consists of a CH3 domain or portion thereof. In another embodiment, an Fc domain consists of a hinge domain (or portion thereof) and a CH3 domain (or portion thereof). In another embodiment, an Fc domain consists of a CH2 domain (or portion thereof) and a CH3 domain. In another embodiment, an Fc domain consists of a hinge domain (or portion thereof) and a CH2 domain (or portion thereof). In one embodiment, an Fc domain lacks at least a portion of a CH2 domain (e.g., all or part of a CH2 domain). In one embodiment, an Fc domain of the invention comprises at least the portion of an Fc molecule known in the art to be required for FcRn binding. In one embodiment, an Fc domain of the invention comprises at least the portion of an Fc molecule known in the art to be required for Protein A binding. In one embodiment, an Fc domain of the invention comprises at least the portion of an Fc molecule known in the art to be required for protein G binding. An Fc domain herein generally refers to a polypeptide comprising all or part of the Fc domain of an immunoglobulin heavy-chain. This includes, but is not limited to, polypeptides comprising the entire CHI, hinge, CH2, and / or CH3 domains as well as fragments of such peptides comprising only, e.g., the hinge, CH2, and CH3 domain. The Fc domain may be derived from an immunoglobulin of any species and / or any subtype, including, but not limited to, a human IgGl, IgG2, IgG3, IgG4, IgD, IgA, IgE, or IgM antibody. The Fc domain encompasses native Fc and Fc variant molecules. As with Fc variants and native Fc's, the term Fc domain includes molecules in monomeric or multimeric form, whether digested from whole antibody or produced by other means. As set forth herein, it will be understood by one of ordinary skill in the art that any Fc domain may be modified such that it varies in amino acid sequence from the native Fc domain of a naturally occurring immunoglobulin molecule. The Fc domains of a nuclease agent of the disclosure may be derived from different immunoglobulin molecules. For example, an Fc domain of a nuclease agent may comprise a CH2 and / or CH3 domain derived from an IgG1 molecule and a hinge region derived from an IgG3 molecule. In another example, an Fc domain can comprise a chimeric hinge region derived, in part, from an IgG1 molecule and, in part, from an IgG3 molecule. In another example, an Fc domain can comprise a chimeric hinge derived, in part, from an IgG1 molecule RVY-02325 and, in part, from an IgG4 molecule. The wild type human IgG1 Fc domain has the amino acid sequence set forth in SEQ ID NO: 20. As used herein, the term “serum half-life” refers to the time required for the in vivo serum nuclease-Fc fusion protein concentration to decline by 50%. The shorter the serum half-life of the nuclease-Fc fusion protein, the shorter time it will have to exert a therapeutic effect. As used herein, the term "nuclease agent" refers to an agent that comprises at least one nuclease domain. In some embodiments, a nuclease agent is a polypeptide. In some embodiments, a nuclease agent comprises a nuclease domain operably linked, with or without a linker, to human serum albumin (HSA). In some embodiments, a nuclease agent comprises a nuclease domain operably linked, with or without a linker, to a glycoprotein. In some embodiments, a nuclease agent comprises a nuclease domain operably linked, with or without a linker, to transferrin. In some embodiment, a nuclease agent comprises one or more nuclease domains operably linked, with or without a linker, to an Fc domain, or a variant or fragment thereof, and nucleic acids encoding such polypeptides. In some embodiments, the nuclease agent is a polypeptide that comprises at least two nuclease domains operably linked, with or without a linker, to an Fc domain, or a variant or fragment thereof, and nucleic acids encoding such polypeptides. In some embodiments, the nuclease domain is a human RNase 1. In some embodiments, the nuclease agent is an RNase nuclease agent comprising one or more RNase domains and one or more Fc domains. In some embodiments the nuclease agent is a binuclease agent comprising two or more nuclease domains. In some embodiments, a binuclease agent is a polypeptide comprising two or more nuclease domains and one or more Fc domains. In some embodiments, a binuclease agent comprises one or more RNase-domains, one or more Fc domains, and one or more DNase domains. In some embodiments, a binuclease agent comprises an RNase 1 domain operably linked to the N- or C- terminus of an Fc domain and a DNase domain operably linked to the N- or C- terminus of the Fc domain. In some embodiments, a nuclease agent is a tandem nuclease agent. In some embodiments, a tandem nuclease agent comprises at least two nuclease domains linked in tandem (e.g., from N- to C- terminus). In some embodiments, a tandem nuclease agent comprises a polypeptide that comprises at least two nuclease domains linked in tandem (e.g., from N- to C- terminus) and an Fc domain, or a variant or fragment thereof, and nucleic acids encoding such polypeptides. In some embodiments, a tandem nuclease agent is a polypeptide comprising at least two RNase 1 domains operably linked RVY-02325 in tandem to at least one Fc domain. In some embodiments, a tandem nuclease agent is a polypeptide comprising at least one DNase1 domain and at least one RNase1 domain operably linked in tandem to at least one Fc domain. In some embodiments, a tandem nuclease agent includes from N- to C- terminus a DNase1 domain, a first linker, an RNase1 domain, a second linker, and an Fc domain, or a variant or fragment thereof. As used herein, the term “dimer” refers to a macromolecular complex formed by two macromolecules (e.g., polypeptides). A “homodimer” refers to a dimer that is formed by two identical macromolecules (e.g., polypeptides). A “heterodimer” refers to a dimer that is formed by two different macromolecules (e.g., polypeptides). In some embodiments, the nuclease agent of the disclosure are homodimeric. In some embodiments, the nuclease agent of the disclosure are heterodimeric. As used herein, the term “variant” refers to a polypeptide derived from a wild-type nuclease (e.g., RNase) or Fc domain and differs from the wild-type by one or more alteration(s), i.e., a substitution, insertion, and / or deletion, at one or more positions. A substitution means a replacement of an amino acid occupying a position with a different amino acid. A deletion means removal of an amino acid occupying a position. An insertion means adding 1 or more, such as 1-3 amino acids, immediately adjacent to an amino acid occupying a position. Variant polypeptides necessarily have less than 100% sequence identity or similarity with the wild-type polypeptide. In some embodiments, the variant polypeptide will have an amino acid sequence from about 75% to less than 100% amino acid sequence identity or similarity with the amino acid sequence of wild-type polypeptide, or from about 80% to less than 100%, or from about 85% to less than 100%, or from about 90% to less than 100% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%) or from about 95% to less than 100%, e.g., over the length of the variant polypeptide. As used herein, the terms “subject,” “patient,” and “participant” are used interchangeably. As used herein, the terms “coupled,” “conjugated,” “linked,” “fused,” or “fusion,” are used interchangeably. These terms refer to the joining together of two more elements or components or domains, by whatever means including chemical conjugation or recombinant means. Methods of chemical conjugation (e.g., using heterobifunctional crosslinking agents) are known in the art. RVY-02325 A polypeptide or amino acid sequence "derived from" a designated polypeptide or protein refers to the origin of the polypeptide. Preferably, the polypeptide or amino acid sequence which is derived from a particular sequence has an amino acid sequence that is essentially identical to that sequence or a portion thereof, wherein the portion consists of at least 10-20 amino acids, preferably at least 20-30 amino acids, more preferably at least 30-50 amino acids, or which is otherwise identifiable to one of ordinary skill in the art as having its origin in the sequence. Polypeptides derived from another polypeptide may have one or more mutations relative to the starting polypeptide, e.g., one or more amino acid residues which have been substituted with another amino acid residue or which has one or more amino acid residue insertions or deletions. As used herein, “baseline” refers to a subject’s clinical score (e.g., PROMIS, PGA, PRoF, DSST, and / or FACIT), gene expression in the subject, or a clinical measurement prior to administration of a nuclease agent described herein. Baseline may be on the same day as administration of a nuclease agent to a subject. A subject’s baseline may be measured about one day, about two days, about three days, about four days, about five days, about six days, about one week, about two weeks, about three weeks, about four weeks, or about one month prior to administration of a nuclease agent described herein. In some embodiments, baseline is a subject’s PROMIS score prior to administration of a nuclease agent described herein. In some embodiments, baseline is a subject’s PGA score prior to administration of a nuclease agent described herein. In some embodiments, baseline is a subject’s PRoF score prior to administration of a nuclease agent described herein. In some embodiments, baseline is a subject’s DSST score prior to administration of a nuclease agent described herein. In some embodiments, baseline is a subject’s FACIT score prior to administration of a nuclease agent described herein. In some embodiments, baseline is a subject’s gene expression in a sample (e.g., a blood sample) prior to administration of a nuclease agent described herein. As used herein, the term “interferon protein(s)” or “IFN protein(s)” refers to interferons of any type, e.g., type I interferon, type II interferon, type III interferon. The term interferon protein(s) or IFN protein(s) also refers to interferon subtypes including, but not limited to, interferon alpha (IFN^), interferon beta (IFN^), and interferon gamma (IFN^). An interferon protein may be a human interferon protein or a biologically active fragment thereof. As used herein, genes upregulated or downregulated (i.e., an increase or decrease in expression) in response to one or more interferon proteins refers to interferon-inducible genes. Interferon- RVY-02325 inducible genes refer to genes whose expression is increased or decreased in response to interferon-mediated signaling. For example, binding of interferons to an interferon receptor can trigger the activation of a signaling cascade that is responsible for the induction or suppression of an interferon inducible gene. Signaling cascades and interferon inducible genes are known to those of skill in the art. Methods for determining activation or suppression of these pathways and genes are described herein (e.g., RNA sequencing) and are known to those of skill in the art. The Interferome is an open access database of type I, type II, and type III interferon regulated genes available to those of skill in the art for elucidating interferon-mediated signaling (e.g., IFN^ and IFN^ signaling). Rusinova, I. et al., INTERFEROME v2.0: an updated database of annotated interferon-regulated genes. Nucleic Acids Research.2013 January; 41 (database issue): D1040- D1046. Exemplary interferon-mediated signaling cascades and genes can be found in, but are not limited to, Schoggins, J.W., Interferon-Stimulated Genes: What Do They All Do?; Annual Review of Virology. vol 6:567-584, July 5, 2019; Schneider, W.M., et al. Interferon-Stimulated Genes: A complex Web of Host Defenses; Annu Rev Immunol. 32:513–545, Feb 6, 2014. Interferon gamma mediated signaling and interferon gamma inducible genes include, but are not limited to those found in Bhat, M.Y., et al. Comprehensive network map of interferon gamma signaling. J Cell Commun Signal. 12(4):745–751, Sep 6, 2018. SARS-CoV Infection In some embodiments, a nuclease agent of the disclosure (for example, an RNase-Fc fusion protein) is administered to subjects (for example, human subjects) and treats symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, a nuclease agent of the disclosure is administered to subjects (for example, human subjects) and digests circulating RNA in the subjects (for example, circulating SARS-CoV viral RNA (e.g., circulating SARS-CoV-1 and / or SARS-CoV-2 viral RNA)). In some embodiments, a nuclease agent of the disclosure is administered to subjects (for example, human subjects) and digests circulating viral RNA (for example, circulating SARS-CoV viral RNA (e.g., circulating SARS-CoV-1 and / or SARS-CoV-2 viral RNA)) in the subjects and thereby reduces symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV- 2) viral infection include, but are not limited to, fatigue, reduced cognitive function, cognitive RVY-02325 impairment, brain fog, depression, concentration difficulties, hypercytokinemia, and inflammation. In some embodiments, a symptom associated with a SARS-CoV (e.g., SARS- CoV-1 and / or SARS-CoV-2) viral infection is fatigue. In some embodiments, a symptom associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is reduced cognitive function. In some embodiments, a symptom associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is inflammation. In some embodiments, a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is an acute SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is a latent SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is a chronic SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is a prior SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, a SARS-CoV infection is a SARS-CoV-1 infection. In some embodiments, a SARs-CoV infection is a SARS-CoV-2 infection. In some embodiments, the SARS-CoV virus is a mutated variant of SARS-CoV-1. In some embodiments, the SARS-CoV virus is a mutated variant of SARS-CoV-2. In some embodiments, a SARS-CoV infection is a variant SARS-CoV infection. In some embodiments, a SARS-CoV infection is a variant SARS- CoV-1 infection. In some embodiments, a SARS-CoV infection is a variant SARS-CoV-2 infection. In some embodiments, a SARS-CoV infection is a mutant SARS-CoV infection. In some embodiments, a SARS-CoV infection is a mutant SARS-CoV-1 infection. In some embodiments, a SARS-CoV infection is a mutant SARS-CoV-2 infection. In some embodiments, a SARS-CoV infection is an infection by a coronavirus. In some embodiments, the SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) infection is an acute infection. In some embodiments, the symptoms associated with the SARS- CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection are acute symptoms. In some embodiments, acute symptoms persist for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 days. In some embodiments, acute symptoms persist for 1 day to at least 3 weeks. In some embodiments, acute symptoms persist for 1 day and up to 3 weeks. RVY-02325 In some embodiments, the symptoms associated with the SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection are long-term symptoms. In some embodiments, the symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection are from a prior infection. In some embodiments, the long-term symptoms persist for at least 21 days, at least 28 days, at least 35 days, at least 42 days, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 24 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 1 year, at least 2 years, or at least 2 years. In some embodiments, the long-term symptoms persist for 1 week to 1 year or longer. In some embodiments, the long-term symptoms persist for at least 24 weeks. In some embodiments, the long-term symptoms persist for at least 1 year. In some embodiments, the long-term symptoms persist for 1 year or longer. In some embodiments, the long-term symptoms persist for 2 years or longer. In some embodiments, the long-term symptoms persist for 3 years or longer. In some embodiments, the symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection include fatigue. In some embodiments, the symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection include cognitive impairment. In some embodiments, the symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection include reduced cognitive function. In some embodiments, the cognitive impairment or reduced cognitive function is brain fog. In some embodiments, the cognitive impairment or reduced cognitive function is depression. In some embodiments, the symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) virus infection include brain fog. In some embodiments, the symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection include depression. In some embodiments, the symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection include concentration difficulties. In some embodiments, the symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection include inflammation. In some embodiments, the symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection include hypercytokinemia (“cytokine storm”). In some embodiments, the symptoms associated with SARS-CoV (e.g., SARS-CoV-1 RVY-02325 and / or SARS-CoV-2) virus infection include one or more of shortness of breath / difficulty breathing, muscle or body aches, headache, loss of taste or smell, sore throat, congestion, nausea, vomiting, diarrhea, inability to wake, inability to stay awake, or confusion. In some embodiments, a symptom associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection is fatigue. In some embodiments, a symptom associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection is cognitive impairment. In some embodiments, a symptom associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) virus infection is reduced cognitive function. In some embodiments, the cognitive impairment or reduced cognitive function is brain fog. In some embodiments, the cognitive impairment or reduced cognitive function is depression. In some embodiments, a symptom associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection is brain fog. In some embodiments, a symptom associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection is depression. In some embodiments, a symptom associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection is concentration difficulties. In some embodiments, a symptom associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection is inflammation. In some embodiments, a symptom associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection is hypercytokinemia i.e.., “cytokine storm”. In some embodiments, the symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection include one or more of shortness of breath / difficulty breathing, muscle or body aches, headache, loss of taste or smell, sore throat, congestion, nausea, vomiting, diarrhea, inability to wake, inability to stay awake, or confusion. Hypercytokinemia also referred to herein as “cytokine storm”, is a reaction in the human body to an infection that releases pro-inflammatory molecules. Some patients with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) infection develop cytokine storm upon infection. The development of cytokine storm increases inflammation in a patient with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, hypercytokinemia occurs in a subject with SARS-CoV viral infection. In some embodiments, a nuclease agent described herein digests circulating SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral RNA in a subject. In some embodiments, the disclosure provides a method of reducing hypercytokinemia in a subject with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral RVY-02325 infection by treating the subject with a nuclease agent described herein. In some embodiments, a nuclease agent of the disclosure is administered to a human subject in need thereof to reduce hypercytokinemia in a subject with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, a nuclease agent of the disclosure, is administered to a human subject in need thereof to reduce hypercytokinemia and inflammation in a subject with SARS- CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, an inflammatory response occurs in a patient infected with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the inflammatory response is elevated in a patient following SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, a nuclease agent described herein digests circulating SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral RNA in a subject. In some embodiments, a nuclease agent described herein digests circulating SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral RNA and reduces inflammation in a subject. Biochemical Assays In some embodiments, a nuclease agent of the disclosure is administered to human patients in need thereof to treat symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is an acute infection. In some embodiments, a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is a prior infection. In some aspects, the effectiveness of a nuclease agent is demonstrated by comparing (for example, by RNA-Seq) the expression of inflammatory genes (for example, known panels of IFN-regulated genes (Chiche et al)) and / or comparing circulating viral RNA levels in human patients treated with a nuclease agent disclosed herein compared to placebo. For example, a human subject in need of treatment is selected or identified (e.g., a patient with symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection). The subject can be in need of, e.g., reducing a cause or symptom of SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the subject is a female subject. In some embodiments, the patient has symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection and is in need of reducing fatigue. In some embodiments, the patient has symptoms associated with SARS-CoV (e.g., SARS-CoV-1 RVY-02325 and / or SARS-CoV-2) virus infection and is in need of reducing inflammation. In some embodiments, the patient has symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection and is in need of reducing brain fog. In some embodiments, the patient has symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection and is in need of reducing cognitive impairment. In some embodiments, the patient has symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection and is in need of improving cognitive function. In some embodiments, the patient has symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection and is in need of reducing depression. In some embodiments, the patient has symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection and is in need of reducing hypercytokinemia. In some embodiments, the patient has symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection and is in need of improving concentration (for example, reducing concentration difficulties) The identification of the subject can occur in a clinical setting, or elsewhere, e.g., in the subject's home through the subject's own use of a self-testing kit. In some embodiments, SARS-CoV RNA qualitative RT- PCR is used to diagnose a subject with a SARS-CoV infection. In some embodiments, an antigen test is used to diagnose a subject with a SARS-CoV infection. In some embodiments, SARS- CoV-2 RNA qualitative RT-PCR is used to diagnose a subject with a SARS-CoV-2 infection. In some embodiments, an antigen test is used to diagnose a subject with a SARS-CoV-2 infection. In some embodiments, a subject is diagnosed with a SARS-Co-V viral infection during an acute infection. In some embodiments, a subject is diagnosed as having had a prior SARS-CoV infection. In some embodiments, a subject is diagnosed with a SARS-CoV infection about 168 days to about 365 days after the acute infection. In some embodiments, the subject has had symptoms associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 1 month to about 3 years or longer. In some embodiments, the subject has had symptoms associated with post-acute sequelae of SARS-CoV- 2 infection (PASC) for about 1 year to about 3 years. In some embodiments, the subject has had symptoms associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 1 year to about 2 years. In some embodiments, the subject has had symptoms associated with post- acute sequelae of SARS-CoV-2 infection (PASC) for about 6 months to about 12 months. In some embodiments, the subject has had symptoms associated with post-acute sequelae of SARS- RVY-02325 CoV-2 infection (PASC) for about 6 months to about 9 months. In some embodiments, the subject has had symptoms associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 9 months to about 12 months. In some embodiments, the subject has had symptoms associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 3 months to about 6 months. In some embodiments, the subject has had symptoms associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 1 month to about 3 months. In some embodiments, the subject has had symptoms associated with post-acute sequelae of SARS- CoV-2 infection (PASC) for about 12 months. In some embodiments, the subject has had symptoms associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 6 months. In some embodiments, the subject has had symptoms associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 6 months to about 3 months. In some embodiments, at baseline (day 1), a suitable first dose of a nuclease agent of the disclosure is administered to the patient in need thereof. In some embodiments the nuclease agent is formulated as described herein. In some embodiments, the patient’s condition is evaluated at baseline (day 1) and after a period of time following the first dose, e.g., day 8, day 15, day 29, day 43, day 57, day 71, day 85, day 99 or at the end of the study, e.g., by measuring the levels of inflammatory markers (for example, inflammation-related genes), anti-nuclear antibodies (ANA), anti-phospholipid antibodies, serum ferritin,and / or C-reactive protein. Other relevant criteria can also be measured. In some embodiments, measurements are evaluated with immunoassay techniques known to those with skill in the art. Immunoassays can include but are not limited to, enzyme-linked immunosorbent assays ELISA), enzyme multiplied immunoassay technique (EMIT), radioimmunoassay (RIA), and real-time quantitative polymerase chain reaction (RT qPCR), The number and strength of doses are adjusted according to the subject's needs. After treatment, the subject's C-reactive protein, serum ferritin, and other inflammatory markers including the expression of inflammation-related genes are improved relative to the levels existing prior to the treatment and are more comparable to the levels in a healthy subject, or relative to the levels measured in a similarly afflicted but untreated / control subject. In some embodiments, c-reactive protein (CRP) is measured in a patient with symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection. In some embodiments, CRP is increased in a patient with SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) virus infection. In some embodiments, the disclosure provides a method of reducing RVY-02325 CRP in a patient with symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) virus infection by treating with a nuclease agent described herein. In some embodiments, a nuclease agent of the disclosure is administered to human patients in need thereof to reduce CRP levels in a patient with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection. In some embodiments, after treatment, serum CRP levels are reduced by at least 5% to at least 100% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 10% to at least 90% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 5% to at least 80% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 10% to at least 80% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 5% to at least 75% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 10% to at least 75% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 5% to at least 50% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 10% to at least 50% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 5% to at least 40% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 10% to at least 40% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 5% to at least 30% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 10% to at least 30% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 5% to at least 20% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 10% to at least 20% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 10% to at least 15% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 5% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 10% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 15% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 20% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 25% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 30% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 40% in the subject. In some RVY-02325 embodiments, after treatment, serum CRP levels are reduced by at least 50% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 60% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 70% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 80% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 90% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 99% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by at least 100% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 5% to about 100% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 10% to about 90% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 5% to about 80% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 10% to about 80% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 5% to about 75% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 10% to about 75% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 5% to about 50% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 10% to about 50% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 5% to about 40% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 10% to about 40% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 5% to about 30% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 10% to about 30% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 5% to about 20% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 10% to about 20% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 10% to about 15% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 5% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 10% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 15% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 20% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by RVY-02325 about 25% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 30% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 40% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 50% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 60% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 70% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 80% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 90% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 99% in the subject. In some embodiments, after treatment, serum CRP levels are reduced by about 100% in the subject. In some embodiments, anti-nuclear antibodies (ANA) are measured in a patient with symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection. In some embodiments, ANA are detected in a patient with SARS-CoV at baseline. In some embodiments, the disclosure provides a method of reducing CRP in an ANA positive patient with symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection by treating with a nuclease agent described herein. In some embodiments, the disclosure provides a method of reducing serum ferritin levels in an ANA positive patient with symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection by treating with a nuclease agent described herein In some embodiments, serum ferritin is measured in a patient with symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection. In some embodiments, serum ferritin levels are increased in a patient with SARS-CoV (e.g., SARS-CoV- 1 and / or SARS-CoV-2) virus infection. In some embodiments, the disclosure provides a method of reducing serum ferritin in a patient with symptoms associated with SARS-CoV (e.g., SARS- CoV-1 and / or SARS-CoV-2) virus infection by treating with a nuclease agent described herein. In some embodiments, a nuclease agent of the disclosure is administered to human patients in need thereof to reduce serum ferritin in a patient with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection. In some embodiments, after treatment, serum ferritin levels are reduced by at least 5% to at least 100% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 10% to at least 90% in the subject. In some embodiments, after treatment, RVY-02325 serum ferritin levels are reduced by at least 5% to at least 80% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 10% to at least 80% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 5% to at least 75% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 10% to at least 75% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 5% to at least 50% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 10% to at least 50% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 5% to at least 40% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 10% to at least 40% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 5% to at least 30% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 10% to at least 30% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 5% to at least 20% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 10% to at least 20% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 10% to at least 15% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 5% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 10% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 15% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 20% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 25% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 30% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 40% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 50% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 60% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 70% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 80% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 90% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by at least 99% in the subject. In RVY-02325 some embodiments, after treatment, serum ferritin levels are reduced by at least 100% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 5% to about 100% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 10% to about 90% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 5% to about 80% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 10% to about 80% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 5% to about 75% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 10% to about 75% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 5% to about 50% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 10% to about 50% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 5% to about 40% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 10% to about 40% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 5% to about 30% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 10% to about 30% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 5% to about 20% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 10% to about 20% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 10% to about 15% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 5% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 10% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 15% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 20% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 25% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 30% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 40% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 50% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 60% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 70% in the subject. In some RVY-02325 embodiments, after treatment, serum ferritin levels are reduced by about 80% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 90% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 99% in the subject. In some embodiments, after treatment, serum ferritin levels are reduced by about 100% in the subject. Assaying Gene Expression Profiles In some embodiments, a nuclease agent of the disclosure is administered to human subjects in need thereof to treat symptoms associated with SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, treatment with a nuclease agent of the disclosure results in an increase or decrease in expression of one or more genes in response to one or more interferon proteins. In some embodiments, treatment with a nuclease agent of the disclosure to a female subject results in an increase or decrease in expression of one or more genes in response to one or more interferon proteins. In some embodiments, the one or more interferon proteins are alpha interferon proteins. In some embodiments, the interferon protein is IFN^. In some embodiments, the one or more interferon proteins are gamma interferon proteins. In some embodiments, the interferon protein is IFN^. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more genes being upregulated. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more genes being upregulated in response to one or more interferon proteins. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more genes being upregulated in response to one or more alpha interferon proteins. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more genes being upregulated in response to IFN^. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more genes being upregulated in response to one or more gamma interferon proteins. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more genes being upregulated in response to IFN^. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more genes being down regulated. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more genes being down regulated in response to one or more interferon proteins. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more genes RVY-02325 being down regulated in response to one or more alpha interferon proteins. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more genes being down regulated in response to IFN^. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more genes being down regulated in response to one or more gamma interferon proteins. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more genes being down regulated in response to IFN^. In some embodiments, treatment with a nuclease agent of the disclosure results in one or more changes of gene expression of a pre-defined gene set. In some embodiments, treatment with a nuclease agent of the disclosure results in an increase in expression of one or more genes in a pre-defined gene set. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in expression of one or more genes in a pre-defined gene set. As used herein, a pre-defined gene set may be a gene set known to those of skill in the art such as one or more gene sets described in the Human Molecular Signatures Database (MSigDB) (see https: / / www.gsea-msigdb.org / gsea / msigdb). MSigDB describes nine major collections and subcollections of human gene sets. The Hallmark gene set includes 50 gene sets which represent specific well-defined biological states or processes. The Hallmark gene sets were generated by a computational methodology based on identifying overlaps between gene sets in various MSigDB collections and retaining genes that display coordinate expression. The Hallmark gene set was first described in Liberzon, A. et al. The Molecular Signatures Database (MSigDB) Hallmark gene set collection. Cell Syst.2015 Dec 23; 1(6):417-425, the contents of while are incorporated herein in their entirety. In some embodiments, the Hallmark gene set is the Interferon Alpha Response gene set which includes genes upregulated in response to alpha interferon proteins. In some embodiments, the Hallmark Interferon Alpha Response gene set includes ADAR, B2M, BATF2, BST2, C1S, CASP1, CASP8, CCRL2, CD47, CD74, CMPK2, CNP, CSF1, CXCL10, CXCL11, DDX60, DHX58, EIF2AK2, ELF1, EPSTI1, FAM125A, FAM46A, FTSJD2, GBP2, GBP4, GMPR, HERC6, HLA-C, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT2, IFIT3, IFITM1, IFITM2, IFITM3, IL15, IL4R, IL7, IRF1, IRF2, IRF7, IRF9, ISG15, ISG20, LAMP3, LAP3, LGALS3BP, LPAR6, LY6E, MOV10, MX1, NCOA7, NMI, NUB1, OAS1, OASL, OGFR, PARP12, PARP14, PARP9, PLSCR1, PNPT1,PRIC285, PROCR, PSMA3, PSMB8, PSMB9, PSME1, PSME2, RIPK2, RNF31, RSAD2, RTP4, SAMD9, SAMD9L, SELL, SLC25A28, RVY-02325 SP110, STAT2, TAP1, TDRD7, TMEM140, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TRIM5, TXNIP, UBA7, UBE2L6, USP18, and WARS. Genes included in the Interferon Alpha Response gene set can be categorized in gene families which share common features such as homology or biochemical activity. Examples include oncogenes, translocated cancer genes, protein kinases, cell differentiation markers, transcription factors, and cytokines and growth factors. In some embodiments, the Hallmark gene set is the Interferon Gamma Response gene set which includes genes upregulated in response to gamma interferon proteins. In some embodiments, the Hallmark Interferon Gamma Response gene set includes ADAR, APOL6, ARID5B, ARL4A, AUTS2, B2M, BANK1, BATF2, BPGM, BST2, BTG1, C1R, C1S, CASP1, CASP3, CASP4, CASP7, CASP8, CCL2, CCL5, CCL7, CD274, CD38, CD40, CD69, CD74, CD86, CDKN1A, CFB, CFH, CIITA, CMKLR1, CMPK2, CSF2RB, CXCL10, CXCL11, CXCL9, DDX58, DDX60, DHX58, EIF2AK2, EIF4E3, EPSTI1, FAS, FCGR1A, FGL2, FPR1, FTSJD2, GBP4, GBP6, GCH1, GPR18, GZMA, HERC6, HIF1A, HLA-A, HLA-B, HLA-DMA, HLA-DQA1, HLA-DRB1, HLA-G, ICAM1, IDO1, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT1, IFIT2, IFIT3, IFITM2, IFITM3, IFNAR2, IL10RA, IL15, IL15RA, IL18BP, IL2RB, IL4R, IL6, IL7, IRF1, IRF2, IRF4, IRF5, IRF7, IRF8, IRF9, ISG15, ISG20, ISOC1, ITGB7, JAK2, KLRK1, LAP3, LATS2, LCP2, LGALS3BP, LY6E, LYSMD2, MARCH1, METTL7B, MT2A, MTHFD2, MVP, MX1, MX2, MYD88, NAMPT, NCOA3, NFKB1, NFKBIA, NLRC5, NMI, NOD1, NUP93, OAS2, OAS3, OASL, OGFR, P2RY14, PARP12, PARP14,PDE4B, PELI1, PFKP, PIM1, PLA2G4A, PLSCR1, PML, PNP, PNPT1, PRIC285, PSMA2, PSMA3, PSMB10, PSMB2, PSMB8, PSMB9, PSME1, PSME2, PTGS2, PTPN1, PTPN2, PTPN6, RAPGEF6, RBCK1, RIPK1, RIPK2, RNF213, RNF31, RSAD2, RTP4, SAMD9L, SAMHD1, SECTM1, SELP, SERPING1, SLAMF7, SLC25A28, SOCS1, SOCS3, SOD2, SP110, SPPL2A, SRI, SSPN, ST3GAL5, ST8SIA4, STAT1, STAT2, STAT3, STAT4, TAP1, TAPBP, TDRD7, TNFAIP2, TNFAIP3, TNFAIP6, TNFSF10, TOR1B, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TXNIP, UBE2L6, UPP1, USP18, VAMP5, VAMP8, VCAM1, WARS, XAF1, XCL1, ZBP1, and ZNFX1.^Genes included in the Interferon Gamma Response gene set can be categorized in gene families which share common features such as homology or biochemical activity. Examples include tumor suppressors, oncogenes, translocated cancer genes, protein kinases, cell differentiation markers, transcription factors, and cytokines and growth factors. RVY-02325 In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene of the Hallmark Interferon Alpha Response gene set in a subject. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene of the Hallmark Interferon Alpha Response gene set in a subject relative to expression of the at least one gene in the subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene of the Hallmark Interferon Alpha Response gene set in a subject relative to expression of the at least one gene in the subject prior to treatment with the nuclease agent, wherein treatment comprises one dose, two doses, three doses, four doses, five doses, six doses, seven doses, eight doses, nine doses, ten doses, eleven doses, or twelve doses of the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene of the Hallmark Interferon Alpha Response gene set in a subject about one week, about two weeks, about three weeks, about four weeks, about five weeks, about six weeks, about seven weeks, about eight weeks, about nine weeks, about ten weeks, about eleven weeks, about twelve weeks, about three months, about four months, about five months, or about six months after a first dose of the nuclease agent relative to expression of the at least one gene in the subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from ADAR, B2M, BATF2, BST2, C1S, CASP1, CASP8, CCRL2, CD47, CD74, CMPK2, CNP, CSF1, CXCL10, CXCL11, DDX60, DHX58, EIF2AK2, ELF1, EPSTI1, FAM125A, FAM46A, FTSJD2, GBP2, GBP4, GMPR, HERC6, HLA-C, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT2, IFIT3, IFITM1, IFITM2, IFITM3, IL15, IL4R, IL7, IRF1, IRF2, IRF7, IRF9, ISG15, ISG20, LAMP3, LAP3, LGALS3BP, LPAR6, LY6E, MOV10, MX1, NCOA7, NMI, NUB1, OAS1, OASL, OGFR, PARP12, PARP14, PARP9, PLSCR1, PNPT1,PRIC285, PROCR, PSMA3, PSMB8, PSMB9, PSME1, PSME2, RIPK2, RNF31, RSAD2, RTP4, SAMD9, SAMD9L, SELL, SLC25A28, SP110, STAT2, TAP1, TDRD7, TMEM140, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TRIM5, TXNIP, UBA7, UBE2L6, USP18, WARS, or any combination thereof, in a subject. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from ADAR, B2M, BATF2, BST2, C1S, CASP1, CASP8, CCRL2, CD47, CD74, CMPK2, CNP, CSF1, CXCL10, CXCL11, DDX60, DHX58, EIF2AK2, ELF1, EPSTI1, FAM125A, FAM46A, FTSJD2, GBP2, GBP4, RVY-02325 GMPR, HERC6, HLA-C, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT2, IFIT3, IFITM1, IFITM2, IFITM3, IL15, IL4R, IL7, IRF1, IRF2, IRF7, IRF9, ISG15, ISG20, LAMP3, LAP3, LGALS3BP, LPAR6, LY6E, MOV10, MX1, NCOA7, NMI, NUB1, OAS1, OASL, OGFR, PARP12, PARP14, PARP9, PLSCR1, PNPT1,PRIC285, PROCR, PSMA3, PSMB8, PSMB9, PSME1, PSME2, RIPK2, RNF31, RSAD2, RTP4, SAMD9, SAMD9L, SELL, SLC25A28, SP110, STAT2, TAP1, TDRD7, TMEM140, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TRIM5, TXNIP, UBA7, UBE2L6, USP18, WARS, or any combination thereof, in a subject relative to expression of the one or more genes in the subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in an increase in at least one gene selected from ADAR, B2M, BATF2, BST2, C1S, CASP1, CASP8, CCRL2, CD47, CD74, CMPK2, CNP, CSF1, CXCL10, CXCL11, DDX60, DHX58, EIF2AK2, ELF1, EPSTI1, FAM125A, FAM46A, FTSJD2, GBP2, GBP4, GMPR, HERC6, HLA-C, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT2, IFIT3, IFITM1, IFITM2, IFITM3, IL15, IL4R, IL7, IRF1, IRF2, IRF7, IRF9, ISG15, ISG20, LAMP3, LAP3, LGALS3BP, LPAR6, LY6E, MOV10, MX1, NCOA7, NMI, NUB1, OAS1, OASL, OGFR, PARP12, PARP14, PARP9, PLSCR1, PNPT1,PRIC285, PROCR, PSMA3, PSMB8, PSMB9, PSME1, PSME2, RIPK2, RNF31, RSAD2, RTP4, SAMD9, SAMD9L, SELL, SLC25A28, SP110, STAT2, TAP1, TDRD7, TMEM140, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TRIM5, TXNIP, UBA7, UBE2L6, USP18, WARS, or any combination thereof, in a subject. In some embodiments, treatment with a nuclease agent of the disclosure results in an increase in at least one gene selected from ADAR, B2M, BATF2, BST2, C1S, CASP1, CASP8, CCRL2, CD47, CD74, CMPK2, CNP, CSF1, CXCL10, CXCL11, DDX60, DHX58, EIF2AK2, ELF1, EPSTI1, FAM125A, FAM46A, FTSJD2, GBP2, GBP4, GMPR, HERC6, HLA-C, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT2, IFIT3, IFITM1, IFITM2, IFITM3, IL15, IL4R, IL7, IRF1, IRF2, IRF7, IRF9, ISG15, ISG20, LAMP3, LAP3, LGALS3BP, LPAR6, LY6E, MOV10, MX1, NCOA7, NMI, NUB1, OAS1, OASL, OGFR, PARP12, PARP14, PARP9, PLSCR1, PNPT1,PRIC285, PROCR, PSMA3, PSMB8, PSMB9, PSME1, PSME2, RIPK2, RNF31, RSAD2, RTP4, SAMD9, SAMD9L, SELL, SLC25A28, SP110, STAT2, TAP1, TDRD7, TMEM140, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TRIM5, TXNIP, UBA7, UBE2L6, USP18, WARS, or any combination thereof, in a subject relative to expression of the one or more genes in the subject prior to treatment with the nuclease agent. RVY-02325 In some embodiments, treatment with a nuclease agent of the disclosure results in an increase or decrease in at least one gene selected from ADAR, B2M, BATF2, BST2, C1S, CASP1, CASP8, CCRL2, CD47, CD74, CMPK2, CNP, CSF1, CXCL10, CXCL11, DDX60, DHX58, EIF2AK2, ELF1, EPSTI1, FAM125A, FAM46A, FTSJD2, GBP2, GBP4, GMPR, HERC6, HLA-C, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT2, IFIT3, IFITM1, IFITM2, IFITM3, IL15, IL4R, IL7, IRF1, IRF2, IRF7, IRF9, ISG15, ISG20, LAMP3, LAP3, LGALS3BP, LPAR6, LY6E, MOV10, MX1, NCOA7, NMI, NUB1, OAS1, OASL, OGFR, PARP12, PARP14, PARP9, PLSCR1, PNPT1,PRIC285, PROCR, PSMA3, PSMB8, PSMB9, PSME1, PSME2, RIPK2, RNF31, RSAD2, RTP4, SAMD9, SAMD9L, SELL, SLC25A28, SP110, STAT2, TAP1, TDRD7, TMEM140, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TRIM5, TXNIP, UBA7, UBE2L6, USP18, WARS, or any combination thereof, in a subject. In some embodiments, treatment with a nuclease agent of the disclosure results in an increase or decrease in at least one gene selected from ADAR, B2M, BATF2, BST2, C1S, CASP1, CASP8, CCRL2, CD47, CD74, CMPK2, CNP, CSF1, CXCL10, CXCL11, DDX60, DHX58, EIF2AK2, ELF1, EPSTI1, FAM125A, FAM46A, FTSJD2, GBP2, GBP4, GMPR, HERC6, HLA-C, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT2, IFIT3, IFITM1, IFITM2, IFITM3, IL15, IL4R, IL7, IRF1, IRF2, IRF7, IRF9, ISG15, ISG20, LAMP3, LAP3, LGALS3BP, LPAR6, LY6E, MOV10, MX1, NCOA7, NMI, NUB1, OAS1, OASL, OGFR, PARP12, PARP14, PARP9, PLSCR1, PNPT1,PRIC285, PROCR, PSMA3, PSMB8, PSMB9, PSME1, PSME2, RIPK2, RNF31, RSAD2, RTP4, SAMD9, SAMD9L, SELL, SLC25A28, SP110, STAT2, TAP1, TDRD7, TMEM140, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TRIM5, TXNIP, UBA7, UBE2L6, USP18, WARS, or any combination thereof, in a subject relative to expression of the one or more genes in the subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from ELF1, TRIM21, TRIM14, RIPK2, OASL, MOV10, TDRD7, STAT2, PNPT1, CD74, PROCR, TRIM26, UBE2L6, IFI44, DDX60, TRAFD1, GBP2, MX1, PSME1, PARP9, USP18, OAS1, NUB1, CMPK2, RTP4, TRIM5, IFIT2, SAMD9L, PARP12, HERC6, CXCL10, CSF1, PARP14, IFIT3, IFI35, LAMP3, IFI44L, RSAD2, ISG15, PSME2, IFIH1, LAP3, EPSTI1, GBP4, BATF2, or any combination thereof, in a subject. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from ELF1, TRIM21, TRIM14, RIPK2, OASL, MOV10, TDRD7, RVY-02325 STAT2, PNPT1, CD74, PROCR, TRIM26, UBE2L6, IFI44, DDX60, TRAFD1, GBP2, MX1, PSME1, PARP9, USP18, OAS1, NUB1, CMPK2, RTP4, TRIM5, IFIT2, SAMD9L, PARP12, HERC6, CXCL10, CSF1, PARP14, IFIT3, IFI35, LAMP3, IFI44L, RSAD2, ISG15, PSME2, IFIH1, LAP3, EPSTI1, GBP4, BATF2, or any combination thereof, in a subject relative to expression of the one or more genes in the subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene of the Hallmark Interferon Gamma Response gene set in a subject. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene of the Hallmark Interferon Gamma Response gene set in a subject relative to expression of the at least one gene in the subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene of the Hallmark Interferon Gamma Response gene set in a subject relative to expression of the at least one gene in the subject prior to treatment with the nuclease agent, wherein treatment comprises one dose, two doses, three doses, four doses, five doses, six doses, seven doses, eight doses, nine doses, ten doses, eleven doses, or twelve doses of the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene of the Hallmark Interferon Gamma Response gene set in a subject about one week, about two weeks, about three weeks, about four weeks, about five weeks, about six weeks, about seven weeks, about eight weeks, about nine weeks, about ten weeks, about eleven weeks, about twelve weeks, about three months, about four months, about five months, or about six months after a first dose of the nuclease agent relative to expression of the at least one gene in the subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from ADAR, APOL6, ARID5B, ARL4A, AUTS2, B2M, BANK1, BATF2, BPGM, BST2, BTG1, C1R, C1S, CASP1, CASP3, CASP4, CASP7, CASP8, CCL2, CCL5, CCL7, CD274, CD38, CD40, CD69, CD74, CD86, CDKN1A, CFB, CFH, CIITA, CMKLR1, CMPK2, CSF2RB, CXCL10, CXCL11, CXCL9, DDX58, DDX60, DHX58, EIF2AK2, EIF4E3, EPSTI1, FAS, FCGR1A, FGL2, FPR1, FTSJD2, GBP4, GBP6, GCH1, GPR18, GZMA, HERC6, HIF1A, HLA-A, HLA-B, HLA-DMA, HLA-DQA1, HLA-DRB1, HLA-G, ICAM1, IDO1, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT1, IFIT2, IFIT3, IFITM2, IFITM3, IFNAR2, IL10RA, IL15, IL15RA, IL18BP, IL2RB, IL4R, IL6, IL7, IRF1, IRF2, IRF4, IRF5, IRF7, IRF8, IRF9, ISG15, RVY-02325 ISG20, ISOC1, ITGB7, JAK2, KLRK1, LAP3, LATS2, LCP2, LGALS3BP, LY6E, LYSMD2, MARCH1, METTL7B, MT2A, MTHFD2, MVP, MX1, MX2, MYD88, NAMPT, NCOA3, NFKB1, NFKBIA, NLRC5, NMI, NOD1, NUP93, OAS2, OAS3, OASL, OGFR, P2RY14, PARP12, PARP14,PDE4B, PELI1, PFKP, PIM1, PLA2G4A, PLSCR1, PML, PNP, PNPT1, PRIC285, PSMA2, PSMA3, PSMB10, PSMB2, PSMB8, PSMB9, PSME1, PSME2, PTGS2, PTPN1, PTPN2, PTPN6, RAPGEF6, RBCK1, RIPK1, RIPK2, RNF213, RNF31, RSAD2, RTP4, SAMD9L, SAMHD1, SECTM1, SELP, SERPING1, SLAMF7, SLC25A28, SOCS1, SOCS3, SOD2, SP110, SPPL2A, SRI, SSPN, ST3GAL5, ST8SIA4, STAT1, STAT2, STAT3, STAT4, TAP1, TAPBP, TDRD7, TNFAIP2, TNFAIP3, TNFAIP6, TNFSF10, TOR1B, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TXNIP, UBE2L6, UPP1, USP18, VAMP5, VAMP8, VCAM1, WARS, XAF1, XCL1, ZBP1, ZNFX1, or any combination thereof, in a subject. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from ADAR, APOL6, ARID5B, ARL4A, AUTS2, B2M, BANK1, BATF2, BPGM, BST2, BTG1, C1R, C1S, CASP1, CASP3, CASP4, CASP7, CASP8, CCL2, CCL5, CCL7, CD274, CD38, CD40, CD69, CD74, CD86, CDKN1A, CFB, CFH, CIITA, CMKLR1, CMPK2, CSF2RB, CXCL10, CXCL11, CXCL9, DDX58, DDX60, DHX58, EIF2AK2, EIF4E3, EPSTI1, FAS, FCGR1A, FGL2, FPR1, FTSJD2, GBP4, GBP6, GCH1, GPR18, GZMA, HERC6, HIF1A, HLA-A, HLA-B, HLA-DMA, HLA-DQA1, HLA-DRB1, HLA-G, ICAM1, IDO1, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT1, IFIT2, IFIT3, IFITM2, IFITM3, IFNAR2, IL10RA, IL15, IL15RA, IL18BP, IL2RB, IL4R, IL6, IL7, IRF1, IRF2, IRF4, IRF5, IRF7, IRF8, IRF9, ISG15, ISG20, ISOC1, ITGB7, JAK2, KLRK1, LAP3, LATS2, LCP2, LGALS3BP, LY6E, LYSMD2, MARCH1, METTL7B, MT2A, MTHFD2, MVP, MX1, MX2, MYD88, NAMPT, NCOA3, NFKB1, NFKBIA, NLRC5, NMI, NOD1, NUP93, OAS2, OAS3, OASL, OGFR, P2RY14, PARP12, PARP14,PDE4B, PELI1, PFKP, PIM1, PLA2G4A, PLSCR1, PML, PNP, PNPT1, PRIC285, PSMA2, PSMA3, PSMB10, PSMB2, PSMB8, PSMB9, PSME1, PSME2, PTGS2, PTPN1, PTPN2, PTPN6, RAPGEF6, RBCK1, RIPK1, RIPK2, RNF213, RNF31, RSAD2, RTP4, SAMD9L, SAMHD1, SECTM1, SELP, SERPING1, SLAMF7, SLC25A28, SOCS1, SOCS3, SOD2, SP110, SPPL2A, SRI, SSPN, ST3GAL5, ST8SIA4, STAT1, STAT2, STAT3, STAT4, TAP1, TAPBP, TDRD7, TNFAIP2, TNFAIP3, TNFAIP6, TNFSF10, TOR1B, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TXNIP, UBE2L6, UPP1, USP18, VAMP5, VAMP8, VCAM1, WARS, XAF1, XCL1, RVY-02325 ZBP1, ZNFX1, or any combination thereof, in a subject relative to expression of the at least one gene in the subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in an increase in at least one gene selected from ADAR, APOL6, ARID5B, ARL4A, AUTS2, B2M, BANK1, BATF2, BPGM, BST2, BTG1, C1R, C1S, CASP1, CASP3, CASP4, CASP7, CASP8, CCL2, CCL5, CCL7, CD274, CD38, CD40, CD69, CD74, CD86, CDKN1A, CFB, CFH, CIITA, CMKLR1, CMPK2, CSF2RB, CXCL10, CXCL11, CXCL9, DDX58, DDX60, DHX58, EIF2AK2, EIF4E3, EPSTI1, FAS, FCGR1A, FGL2, FPR1, FTSJD2, GBP4, GBP6, GCH1, GPR18, GZMA, HERC6, HIF1A, HLA-A, HLA-B, HLA-DMA, HLA-DQA1, HLA-DRB1, HLA-G, ICAM1, IDO1, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT1, IFIT2, IFIT3, IFITM2, IFITM3, IFNAR2, IL10RA, IL15, IL15RA, IL18BP, IL2RB, IL4R, IL6, IL7, IRF1, IRF2, IRF4, IRF5, IRF7, IRF8, IRF9, ISG15, ISG20, ISOC1, ITGB7, JAK2, KLRK1, LAP3, LATS2, LCP2, LGALS3BP, LY6E, LYSMD2, MARCH1, METTL7B, MT2A, MTHFD2, MVP, MX1, MX2, MYD88, NAMPT, NCOA3, NFKB1, NFKBIA, NLRC5, NMI, NOD1, NUP93, OAS2, OAS3, OASL, OGFR, P2RY14, PARP12, PARP14,PDE4B, PELI1, PFKP, PIM1, PLA2G4A, PLSCR1, PML, PNP, PNPT1, PRIC285, PSMA2, PSMA3, PSMB10, PSMB2, PSMB8, PSMB9, PSME1, PSME2, PTGS2, PTPN1, PTPN2, PTPN6, RAPGEF6, RBCK1, RIPK1, RIPK2, RNF213, RNF31, RSAD2, RTP4, SAMD9L, SAMHD1, SECTM1, SELP, SERPING1, SLAMF7, SLC25A28, SOCS1, SOCS3, SOD2, SP110, SPPL2A, SRI, SSPN, ST3GAL5, ST8SIA4, STAT1, STAT2, STAT3, STAT4, TAP1, TAPBP, TDRD7, TNFAIP2, TNFAIP3, TNFAIP6, TNFSF10, TOR1B, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TXNIP, UBE2L6, UPP1, USP18, VAMP5, VAMP8, VCAM1, WARS, XAF1, XCL1, ZBP1, ZNFX1, or any combination thereof, in a subject. In some embodiments, treatment with a nuclease agent of the disclosure results in an increase in at least one gene selected from ADAR, APOL6, ARID5B, ARL4A, AUTS2, B2M, BANK1, BATF2, BPGM, BST2, BTG1, C1R, C1S, CASP1, CASP3, CASP4, CASP7, CASP8, CCL2, CCL5, CCL7, CD274, CD38, CD40, CD69, CD74, CD86, CDKN1A, CFB, CFH, CIITA, CMKLR1, CMPK2, CSF2RB, CXCL10, CXCL11, CXCL9, DDX58, DDX60, DHX58, EIF2AK2, EIF4E3, EPSTI1, FAS, FCGR1A, FGL2, FPR1, FTSJD2, GBP4, GBP6, GCH1, GPR18, GZMA, HERC6, HIF1A, HLA-A, HLA-B, HLA-DMA, HLA-DQA1, HLA-DRB1, HLA-G, ICAM1, IDO1, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT1, IFIT2, IFIT3, IFITM2, IFITM3, IFNAR2, IL10RA, IL15, IL15RA, IL18BP, IL2RB, RVY-02325 IL4R, IL6, IL7, IRF1, IRF2, IRF4, IRF5, IRF7, IRF8, IRF9, ISG15, ISG20, ISOC1, ITGB7, JAK2, KLRK1, LAP3, LATS2, LCP2, LGALS3BP, LY6E, LYSMD2, MARCH1, METTL7B, MT2A, MTHFD2, MVP, MX1, MX2, MYD88, NAMPT, NCOA3, NFKB1, NFKBIA, NLRC5, NMI, NOD1, NUP93, OAS2, OAS3, OASL, OGFR, P2RY14, PARP12, PARP14,PDE4B, PELI1, PFKP, PIM1, PLA2G4A, PLSCR1, PML, PNP, PNPT1, PRIC285, PSMA2, PSMA3, PSMB10, PSMB2, PSMB8, PSMB9, PSME1, PSME2, PTGS2, PTPN1, PTPN2, PTPN6, RAPGEF6, RBCK1, RIPK1, RIPK2, RNF213, RNF31, RSAD2, RTP4, SAMD9L, SAMHD1, SECTM1, SELP, SERPING1, SLAMF7, SLC25A28, SOCS1, SOCS3, SOD2, SP110, SPPL2A, SRI, SSPN, ST3GAL5, ST8SIA4, STAT1, STAT2, STAT3, STAT4, TAP1, TAPBP, TDRD7, TNFAIP2, TNFAIP3, TNFAIP6, TNFSF10, TOR1B, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TXNIP, UBE2L6, UPP1, USP18, VAMP5, VAMP8, VCAM1, WARS, XAF1, XCL1, ZBP1, ZNFX1, or any combination thereof, in a subject relative to expression of the at least one gene in the subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in an increase or decrease in at least one gene selected from ADAR, APOL6, ARID5B, ARL4A, AUTS2, B2M, BANK1, BATF2, BPGM, BST2, BTG1, C1R, C1S, CASP1, CASP3, CASP4, CASP7, CASP8, CCL2, CCL5, CCL7, CD274, CD38, CD40, CD69, CD74, CD86, CDKN1A, CFB, CFH, CIITA, CMKLR1, CMPK2, CSF2RB, CXCL10, CXCL11, CXCL9, DDX58, DDX60, DHX58, EIF2AK2, EIF4E3, EPSTI1, FAS, FCGR1A, FGL2, FPR1, FTSJD2, GBP4, GBP6, GCH1, GPR18, GZMA, HERC6, HIF1A, HLA-A, HLA-B, HLA-DMA, HLA-DQA1, HLA-DRB1, HLA-G, ICAM1, IDO1, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT1, IFIT2, IFIT3, IFITM2, IFITM3, IFNAR2, IL10RA, IL15, IL15RA, IL18BP, IL2RB, IL4R, IL6, IL7, IRF1, IRF2, IRF4, IRF5, IRF7, IRF8, IRF9, ISG15, ISG20, ISOC1, ITGB7, JAK2, KLRK1, LAP3, LATS2, LCP2, LGALS3BP, LY6E, LYSMD2, MARCH1, METTL7B, MT2A, MTHFD2, MVP, MX1, MX2, MYD88, NAMPT, NCOA3, NFKB1, NFKBIA, NLRC5, NMI, NOD1, NUP93, OAS2, OAS3, OASL, OGFR, P2RY14, PARP12, PARP14,PDE4B, PELI1, PFKP, PIM1, PLA2G4A, PLSCR1, PML, PNP, PNPT1, PRIC285, PSMA2, PSMA3, PSMB10, PSMB2, PSMB8, PSMB9, PSME1, PSME2, PTGS2, PTPN1, PTPN2, PTPN6, RAPGEF6, RBCK1, RIPK1, RIPK2, RNF213, RNF31, RSAD2, RTP4, SAMD9L, SAMHD1, SECTM1, SELP, SERPING1, SLAMF7, SLC25A28, SOCS1, SOCS3, SOD2, SP110, SPPL2A, SRI, SSPN, ST3GAL5, ST8SIA4, STAT1, STAT2, STAT3, STAT4, TAP1, TAPBP, TDRD7, RVY-02325 TNFAIP2, TNFAIP3, TNFAIP6, TNFSF10, TOR1B, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TXNIP, UBE2L6, UPP1, USP18, VAMP5, VAMP8, VCAM1, WARS, XAF1, XCL1, ZBP1, ZNFX1, or any combination thereof, in a subject. In some embodiments, treatment with a nuclease agent of the disclosure results in an increase or decrease in at least one gene selected from ADAR, APOL6, ARID5B, ARL4A, AUTS2, B2M, BANK1, BATF2, BPGM, BST2, BTG1, C1R, C1S, CASP1, CASP3, CASP4, CASP7, CASP8, CCL2, CCL5, CCL7, CD274, CD38, CD40, CD69, CD74, CD86, CDKN1A, CFB, CFH, CIITA, CMKLR1, CMPK2, CSF2RB, CXCL10, CXCL11, CXCL9, DDX58, DDX60, DHX58, EIF2AK2, EIF4E3, EPSTI1, FAS, FCGR1A, FGL2, FPR1, FTSJD2, GBP4, GBP6, GCH1, GPR18, GZMA, HERC6, HIF1A, HLA-A, HLA-B, HLA-DMA, HLA-DQA1, HLA-DRB1, HLA-G, ICAM1, IDO1, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT1, IFIT2, IFIT3, IFITM2, IFITM3, IFNAR2, IL10RA, IL15, IL15RA, IL18BP, IL2RB, IL4R, IL6, IL7, IRF1, IRF2, IRF4, IRF5, IRF7, IRF8, IRF9, ISG15, ISG20, ISOC1, ITGB7, JAK2, KLRK1, LAP3, LATS2, LCP2, LGALS3BP, LY6E, LYSMD2, MARCH1, METTL7B, MT2A, MTHFD2, MVP, MX1, MX2, MYD88, NAMPT, NCOA3, NFKB1, NFKBIA, NLRC5, NMI, NOD1, NUP93, OAS2, OAS3, OASL, OGFR, P2RY14, PARP12, PARP14,PDE4B, PELI1, PFKP, PIM1, PLA2G4A, PLSCR1, PML, PNP, PNPT1, PRIC285, PSMA2, PSMA3, PSMB10, PSMB2, PSMB8, PSMB9, PSME1, PSME2, PTGS2, PTPN1, PTPN2, PTPN6, RAPGEF6, RBCK1, RIPK1, RIPK2, RNF213, RNF31, RSAD2, RTP4, SAMD9L, SAMHD1, SECTM1, SELP, SERPING1, SLAMF7, SLC25A28, SOCS1, SOCS3, SOD2, SP110, SPPL2A, SRI, SSPN, ST3GAL5, ST8SIA4, STAT1, STAT2, STAT3, STAT4, TAP1, TAPBP, TDRD7, TNFAIP2, TNFAIP3, TNFAIP6, TNFSF10, TOR1B, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TXNIP, UBE2L6, UPP1, USP18, VAMP5, VAMP8, VCAM1, WARS, XAF1, XCL1, ZBP1, ZNFX1, or any combination thereof, in a subject relative to expression of the at least one gene in the subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in one or more of PTPN1, HLA-A, TRIM21, TRIM14, RIPK2, VAMP5, PFKP, GBP6, SLAMF7, OASL, HIF1A, TDRD7, PTGS2, STAT2, PNPT1, IL18BP, CASP3, FGL2, EIF4E3, HLA-DRB1, VCAM1, NCOA3, GPR18, CD74, GCH1, NUP93, TRIM26, PSMA2, UBE2L6, CD86, CCL5, CFH, IFI44, PSMB2, RNF213, XAF1, DDX60, TRAFD1, MX1, PSME1, ST3GAL5, USP18, LCP2, FCGR1A, CMPK2, RTP4, CDKN1A, OAS2, P2RY14, CXCL9, RVY-02325 IFIT2, SAMD9L, PARP12, HERC6, OAS3, IRF4, IFIT1, CXCL10, SAMHD1, SERPING1, PARP14, IFIT3, IFI35, SOCS3, PML, IFI44L, RSAD2, ISG15, PSME2, IFIH1, LAP3, EPSTI1, CD274, IDO1, GBP4, STAT1, APOL6, BATF2, or any combination thereof, in a subject. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from ELF1, TRIM21, TRIM14, RIPK2, OASL, MOV10, TDRD7, STAT2, PNPT1, CD74, PROCR, TRIM26, UBE2L6, IFI44, DDX60, TRAFD1, GBP2, MX1, PSME1, PARP9, USP18, OAS1, NUB1, CMPK2, RTP4, TRIM5, IFIT2, SAMD9L, PARP12, HERC6, CXCL10, CSF1, PARP14, IFIT3, IFI35, LAMP3, IFI44L, RSAD2, ISG15, PSME2, IFIH1, LAP3, EPSTI1, GBP4, BATF2, or any combination thereof, in a subject relative to expression of the at least one gene in the subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene of the Hallmark Interferon Alpha Response gene set in a female subject. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene of the Hallmark Interferon Alpha Response gene set in a female subject relative to expression of the at least one gene in the female subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease at least one gene selected from ADAR, B2M, BATF2, BST2, C1S, CASP1, CASP8, CCRL2, CD47, CD74, CMPK2, CNP, CSF1, CXCL10, CXCL11, DDX60, DHX58, EIF2AK2, ELF1, EPSTI1, FAM125A, FAM46A,FTSJD2,GBP2,GBP4,GMPR,HERC6,HLA- C,IFI27,IFI30,IFI35,IFI44, IFI44L, IFIH1, IFIT2, IFIT3, IFITM1, IFITM2, IFITM3, IL15, IL4R, IL7, IRF1, IRF2, IRF7, IRF9, ISG15, ISG20, LAMP3, LAP3, LGALS3BP, LPAR6, LY6E, MOV10, MX1, NCOA7, NMI, NUB1, OAS1, OASL, OGFR, PARP12, PARP14, PARP9, PLSCR1, PNPT1,PRIC285, PROCR, PSMA3, PSMB8, PSMB9, PSME1, PSME2, RIPK2, RNF31, RSAD2, RTP4, SAMD9, SAMD9L, SELL, SLC25A28, SP110, STAT2, TAP1, TDRD7, TMEM140, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TRIM5, TXNIP, UBA7, UBE2L6, USP18, WARS, or any combination thereof, in a female subject. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from ADAR, B2M, BATF2, BST2, C1S, CASP1, CASP8, CCRL2, CD47, CD74, CMPK2, CNP, CSF1, CXCL10, CXCL11, DDX60, DHX58, EIF2AK2, ELF1, EPSTI1, FAM125A, FAM46A,FTSJD2,GBP2,GBP4,GMPR,HERC6,HLA-C,IFI27,IFI30,IFI35,IFI44, IFI44L, IFIH1, IFIT2, IFIT3, IFITM1, IFITM2, IFITM3, IL15, IL4R, IL7, IRF1, IRF2, IRF7, RVY-02325 IRF9, ISG15, ISG20, LAMP3, LAP3, LGALS3BP, LPAR6, LY6E, MOV10, MX1, NCOA7, NMI, NUB1, OAS1, OASL, OGFR, PARP12, PARP14, PARP9, PLSCR1, PNPT1,PRIC285, PROCR, PSMA3, PSMB8, PSMB9, PSME1, PSME2, RIPK2, RNF31, RSAD2, RTP4, SAMD9, SAMD9L, SELL, SLC25A28, SP110, STAT2, TAP1, TDRD7, TMEM140, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TRIM5, TXNIP, UBA7, UBE2L6, USP18, WARS, or any combination thereof, in a female subject relative to expression of the at least one gene in the female subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected fromNUB1, PARP12, OASL, MOV10, MX1, TRIM14, UBA7, IFI44, DDX60, PSMB8, USP18, BATF2, IFIH1, GBP4, PSME2, C1S, SLC25A28, NCOA7, RSAD2, CMPK2, LY6E, CSF1, LPAR6, IFI44L, EPSTI1, CXCL10, PSME1, OAS1, LAMP3, TRIM26, LAP3, CD74, CNP, or any combination thereof, in a female subject. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from NUB1, PARP12, OASL, MOV10, MX1, TRIM14, UBA7, IFI44, DDX60, PSMB8, USP18, BATF2, IFIH1, GBP4, PSME2, C1S, SLC25A28, NCOA7, RSAD2, CMPK2, LY6E, CSF1, LPAR6, IFI44L, EPSTI1, CXCL10, PSME1, OAS1, LAMP3, TRIM26, LAP3, CD74, CNP, or any combination thereof, in a female subject relative to expression of the at least one gene in the female subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene of the Hallmark Interferon Gamma Response gene set in a female subject. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene of the Hallmark Interferon Gamma Response gene set in a female subject relative to expression of the at least one gene in the female subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from ADAR, APOL6, ARID5B, ARL4A, AUTS2, B2M, BANK1, BATF2, BPGM, BST2, BTG1, C1R, C1S, CASP1, CASP3, CASP4, CASP7, CASP8, CCL2, CCL5, CCL7, CD274, CD38, CD40, CD69, CD74, CD86, CDKN1A, CFB, CFH, CIITA, CMKLR1, CMPK2, CSF2RB, CXCL10, CXCL11, CXCL9, DDX58, DDX60, DHX58, EIF2AK2, EIF4E3, EPSTI1, FAS, FCGR1A, FGL2, FPR1, FTSJD2, GBP4, GBP6, GCH1, GPR18, GZMA, HERC6, HIF1A, HLA-A, HLA-B, HLA-DMA, HLA-DQA1, HLA-DRB1, HLA-G, ICAM1, IDO1, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT1, IFIT2, RVY-02325 IFIT3, IFITM2, IFITM3, IFNAR2, IL10RA, IL15, IL15RA, IL18BP, IL2RB, IL4R, IL6, IL7, IRF1, IRF2, IRF4, IRF5, IRF7, IRF8, IRF9, ISG15, ISG20, ISOC1, ITGB7, JAK2, KLRK1, LAP3, LATS2, LCP2, LGALS3BP, LY6E, LYSMD2, MARCH1, METTL7B, MT2A, MTHFD2, MVP, MX1, MX2, MYD88, NAMPT, NCOA3, NFKB1, NFKBIA, NLRC5, NMI, NOD1, NUP93, OAS2, OAS3, OASL, OGFR, P2RY14, PARP12, PARP14,PDE4B, PELI1, PFKP, PIM1, PLA2G4A, PLSCR1, PML, PNP, PNPT1, PRIC285, PSMA2, PSMA3, PSMB10, PSMB2, PSMB8, PSMB9, PSME1, PSME2, PTGS2, PTPN1, PTPN2, PTPN6, RAPGEF6, RBCK1, RIPK1, RIPK2, RNF213, RNF31, RSAD2, RTP4, SAMD9L, SAMHD1, SECTM1, SELP, SERPING1, SLAMF7, SLC25A28, SOCS1, SOCS3, SOD2, SP110, SPPL2A, SRI, SSPN, ST3GAL5, ST8SIA4, STAT1, STAT2, STAT3, STAT4, TAP1, TAPBP, TDRD7, TNFAIP2, TNFAIP3, TNFAIP6, TNFSF10, TOR1B, TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TXNIP, UBE2L6, UPP1, USP18, VAMP5, VAMP8, VCAM1, WARS, XAF1, XCL1, ZBP1, ZNFX1, or any combination thereof, in a female subject. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from ADAR, APOL6, ARID5B, ARL4A, AUTS2, B2M, BANK1, BATF2, BPGM, BST2, BTG1, C1R, C1S, CASP1, CASP3, CASP4, CASP7, CASP8, CCL2, CCL5, CCL7, CD274, CD38, CD40, CD69, CD74, CD86, CDKN1A, CFB, CFH, CIITA, CMKLR1, CMPK2, CSF2RB, CXCL10, CXCL11, CXCL9, DDX58, DDX60, DHX58, EIF2AK2, EIF4E3, EPSTI1, FAS, FCGR1A, FGL2, FPR1, FTSJD2, GBP4, GBP6, GCH1, GPR18, GZMA, HERC6, HIF1A, HLA-A, HLA-B, HLA-DMA, HLA-DQA1, HLA-DRB1, HLA-G, ICAM1, IDO1, IFI27, IFI30, IFI35, IFI44, IFI44L, IFIH1, IFIT1, IFIT2, IFIT3, IFITM2, IFITM3, IFNAR2, IL10RA, IL15, IL15RA, IL18BP, IL2RB, IL4R, IL6, IL7, IRF1, IRF2, IRF4, IRF5, IRF7, IRF8, IRF9, ISG15, ISG20, ISOC1, ITGB7, JAK2, KLRK1, LAP3, LATS2, LCP2, LGALS3BP, LY6E, LYSMD2, MARCH1, METTL7B, MT2A, MTHFD2, MVP, MX1, MX2, MYD88, NAMPT, NCOA3, NFKB1, NFKBIA, NLRC5, NMI, NOD1, NUP93, OAS2, OAS3, OASL, OGFR, P2RY14, PARP12, PARP14,PDE4B, PELI1, PFKP, PIM1, PLA2G4A, PLSCR1, PML, PNP, PNPT1, PRIC285, PSMA2, PSMA3, PSMB10, PSMB2, PSMB8, PSMB9, PSME1, PSME2, PTGS2, PTPN1, PTPN2, PTPN6, RAPGEF6, RBCK1, RIPK1, RIPK2, RNF213, RNF31, RSAD2, RTP4, SAMD9L, SAMHD1, SECTM1, SELP, SERPING1, SLAMF7, SLC25A28, SOCS1, SOCS3, SOD2, SP110, SPPL2A, SRI, SSPN, ST3GAL5, ST8SIA4, STAT1, STAT2, STAT3, STAT4, TAP1, TAPBP, TDRD7, TNFAIP2, TNFAIP3, TNFAIP6, TNFSF10, TOR1B, RVY-02325 TRAFD1, TRIM14, TRIM21, TRIM25, TRIM26, TXNIP, UBE2L6, UPP1, USP18, VAMP5, VAMP8, VCAM1, WARS, XAF1, XCL1, ZBP1, ZNFX1, or any combination thereof, in a female subject relative to expression of the at least one gene in the female subject prior to treatment with the nuclease agent. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from IFI35, PML, CFB, STAT4, CD86, VAMP5, LCP2, PARP12, OASL, HLA-B, CXCL9, GPR18, APOL6, VAMP8, ISOC1, PFKP, VCAM1, MX1, TRIM14, NCOA3, RAPGEF6, IFI44, DDX60, CMKLR1, BANK1, GCH1, PSMB8, USP18, NFKB1, BATF2, IFIH1, IFIT1, SLAMF7, HLA-A, OAS2, GBP4, IL2RB, PSME2, SERPING1, C1S, CIITA, CD69, SLC25A28, RSAD2, PTPN1, PTGS2, CMPK2, PSMB10, LY6E, NUP93, C1R, IL6, IFI44L, CFH, EPSTI1, IRF8, CXCL10, IDO1, HLA-DMA, PSME1, ARID5B, MTHFD2, ITGB7, IRF5, SAMHD1, TRIM26, OAS3, SOCS3, IL18BP, LAP3, CD74, HLA- DRB1, PSMB2, IRF4, IL10RA, HLA-DQA1, ST3GAL5, or any combination thereof, in a female subject. In some embodiments, treatment with a nuclease agent of the disclosure results in a decrease in at least one gene selected from IFI35, PML, CFB, STAT4, CD86, VAMP5, LCP2, PARP12, OASL, HLA-B, CXCL9, GPR18, APOL6, VAMP8, ISOC1, PFKP, VCAM1, MX1, TRIM14, NCOA3, RAPGEF6, IFI44, DDX60, CMKLR1, BANK1, GCH1, PSMB8, USP18, NFKB1, BATF2, IFIH1, IFIT1, SLAMF7, HLA-A, OAS2, GBP4, IL2RB, PSME2, SERPING1, C1S, CIITA, CD69, SLC25A28, RSAD2, PTPN1, PTGS2, CMPK2, PSMB10, LY6E, NUP93, C1R, IL6, IFI44L, CFH, EPSTI1, IRF8, CXCL10, IDO1, HLA-DMA, PSME1, ARID5B, MTHFD2, ITGB7, IRF5, SAMHD1, TRIM26, OAS3, SOCS3, IL18BP, LAP3, CD74, HLA- DRB1, PSMB2, IRF4, IL10RA, HLA-DQA1, ST3GAL5, or any combination thereof, in a female subject relative to expression of the at least one gene in the female subject prior to treatment with the nuclease agent. Fatigue Assays Various patient reported outcome (PRO) instruments have been used and validated in the measurement of fatigue in subjects with chronic diseases. Such PROs are known in the art and can be used to assess the efficacy of nuclease agents of the disclosure. Patient Reported Outcome Measurement Information System RVY-02325 The Patient Reported Outcome Measurement Information System (PROMIS) SF 7a is used to measure fatigue in chronic illness based on patient reported symptoms. The PROMIS SF 7a scale is a 7-item questionnaire that measures fatigue on a 5-point Likert scale. A higher SF 7a score indicates more fatigue. Raw scores are converted to a standardized T-score and T scores greater than 50 indicate the presence of fatigue. In some embodiments, the effectiveness of nuclease agents of the disclosure or pharmaceutical compositions thereof is demonstrated by assessing an improvement in fatigue in patients treated with a nuclease agent or pharmaceutical composition thereof. In some embodiments, after treatment, fatigue is generally reduced in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is generally reduced in the patient as measured by PROMIS when compared to the level of fatigue in the patient prior to treatment, and / or when compared to a patient treated with a control formulation. The interpretation of changes in PROMIS scores can be estimated as a minimal important difference (MID) or minimal clinically important improvement (MCII). The MID is defined as the smallest change in score for a particular domain of interest. The MCII is defined as the smallest improvement in a score for a particular domain of interest (see Nordin, Å., Taft, C., Lundgren-Nilsson, Å., & Dencker, A. (2016). Minimal important differences for fatigue patient reported outcome measures-a systematic review. BMC medical research methodology, 16, 62.). In some embodiments, there is a minimal clinically important improvement in fatigue in the subject after treatment with a nuclease agent of the disclosure as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 0.5 standard deviation in T score in the subject as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by 0.5 standard deviation in T score in the subject as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 0.5 to about 1 standard deviations in T score in the subject as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 1 standard deviation in T score in the subject as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 1 to about 1.5 standard deviations in T score in the subject as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 1.5 to about 2 standard deviations in T score in the subject as measured by PROMIS. RVY-02325 In some embodiments, after treatment, fatigue is reduced by at least 1-5 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 6-15 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 1 to 5 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 6 to 15 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by 1 to 5 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by 6 to 15 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 1 point in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 2 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 3 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 4 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 5 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 8 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 10 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 12 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 15 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 20 points in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 100% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 90% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 80% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 80% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 75% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 75% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 50% in the patient as measured by PROMIS. In some embodiments, after treatment, RVY-02325 fatigue is reduced by at least 10% to at least 50% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 40% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 40% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 30% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 30% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 20% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 20% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 5% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 10% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 15% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 20% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 25% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 30% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 40% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 50% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 60% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 70% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 80% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 90% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 99% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by at least 100% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 5% to about 100% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 10% to about 90% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 5% to about 80% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 10% to about 80% in the RVY-02325 patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 5% to about 75% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 10% to about 75% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 5% to about 50% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 10% to about 50% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 5% to about 40% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 10% to about 40% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 5% to about 30% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 10% to about 30% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 5% to about 20% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 10% to about 20% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 5% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 10% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 15% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 20% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 25% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 30% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 40% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 50% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 60% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 70% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 80% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 90% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 99% in the patient as measured by PROMIS. In some embodiments, after treatment, fatigue is reduced by about 100% in the patient as measured by PROMIS. RVY-02325 In some embodiments, the subject experienced moderate or severe fatigue at screening as determined by PROMIS. In some embodiments, the subject experienced fatigue at least 0.5 standard deviations above normal at screening as determined by PROMIS. In some embodiments, the subject experienced fatigue at least 1 standard deviations above normal at screening as determined by PROMIS. In some embodiments, the subject experienced fatigue at least 1.5 standard deviations above normal at screening as determined by PROMIS SF 7a. In some embodiments, the subject experienced fatigue at least 0.5 to 1.5 standard deviations above normal at screening as determined by PROMIS SF 7a. In some embodiments, the patient has a SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) viral infection. In some embodiments, the patient has symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the patient has fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the disclosure provides that PROMIS can be used to measure fatigue in patients with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) viral infection is reduced in a patient treated with a nuclease agent as measured by PROMIS. In some embodiments, fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is reduced in a patient treated with a nuclease agent as measured by PROMIS when compared to the level of fatigue in the patient prior to treatment. In some embodiments, fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) viral infection is reduced in a patient treated with a nuclease agent as measured by PROMIS when compared to the level of fatigue in a patient treated with a control formulation. Physician Global Assessment The Physicians Global Assessment (PGA) is used to an assessment given by physicians to evaluate disease severity in patients based on a 5- or 6-point scale. A higher score indicates higher severity of disease. In some embodiments, an improvement in PGA score can be evaluated as greater than 15% from the starting value. In some embodiments, the effectiveness of nuclease agents of the disclosure or pharmaceutical compositions thereof is demonstrated by assessing an improvement in fatigue in patients treated with a nuclease agent or pharmaceutical composition thereof. In some embodiments, after treatment, fatigue is generally reduced in the RVY-02325 patient as measured by PGA. In some embodiments, after treatment, fatigue is generally reduced in the patient as measured by PGA when compared to the level of fatigue in the patient prior to treatment, and / or when compared to a patient treated with a control formulation. In some embodiments, there is a minimal clinically important improvement in fatigue in the subject after treatment with a nuclease agent of the disclosure as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 1-5 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 1 to 5 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by 1 to 5 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 1 point in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 2 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 3 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 4 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 5 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 20 to 100 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 25 to 60 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 20 to 100 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 25 to 60 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by 20 to 100 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by 25 to 60 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 20 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 25 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 30 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 40 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 50 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 60 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 70 points in the patient as measured by RVY-02325 PGA. In some embodiments, after treatment, fatigue is reduced by about 80 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 90 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 100 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 20 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 25 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 30 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 40 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 50 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 60 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 70 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 80 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 90 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 100 points in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 100% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 90% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 80% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 80% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 75% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 75% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 50% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 50% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 40% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 40% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 30% in RVY-02325 the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 30% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 20% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 20% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 15% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 5% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 10% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 15% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 20% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 25% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 30% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 40% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 50% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 60% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 70% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 80% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 90% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 99% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by at least 100% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 5% to about 100% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 10% to about 90% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 5% to about 80% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 10% to about 80% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 5% to about 75% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 10% to about 75% in the patient as measured by PGA. In some embodiments, RVY-02325 after treatment, fatigue is reduced by about 5% to about 50% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 10% to about 50% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 5% to about 40% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 10% to about 40% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 5% to about 30% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 10% to about 30% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 5% to about 20% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 10% to about 20% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 10% to about 15% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 5% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 10% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 15% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 20% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 25% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 30% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 40% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 50% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 60% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 70% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 80% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 90% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 99% in the patient as measured by PGA. In some embodiments, after treatment, fatigue is reduced by about 100% in the patient as measured by PGA. In some embodiments, the subject experienced moderate or severe fatigue at screening as determined PGA. In some embodiments, the subject experienced fatigue at least 10-15% above normal at screening as determined PGA. RVY-02325 In some embodiments, the patient has a SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) viral infection. In some embodiments, the patient has symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the patient has fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the disclosure provides that PGA can be used to measure fatigue in patients with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) viral infection is reduced in a patient treated with a nuclease agent as measured by PGA. In some embodiments, fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) viral infection is reduced in a patient treated with a nuclease agent as measured by PGA when compared to the level of fatigue in the patient prior to treatment. In some embodiments, fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is reduced in a patient treated with a nuclease agent as measured by PGA when compared to the level of fatigue in a patient treated with a control formulation. FACIT-Fatigue The Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-Fatigue) is used to assess an individual’s level of fatigue during their usual daily activities over the past week. The FACIT-Fatigue questionnaire and Scoring & Interpretation Materials are available from FACIT.org (Elmhurst, Ill., USA). The FACIT-Fatigue questionnaire provides an array of generic and targeted measures. The FACIT fatigue scale has many benefits including high internal validity, high test-retest reliability, reliability and sensitivity to change in patients with a variety of chronic health conditions, ease of use, and use in a variety of settings. (K.F. Tennant, Try This: best Practices in Nursing Care to Older Adults, Issue 30, 2012; Chandran et al., Ann. Rheum. Dis.2007; 66: 936-939). The FACIT-Fatigue is a 13-item questionnaire originally developed to measure fatigue in patients with cancer. The patient is asked to answer 13 questions scored from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). The fatigue scale has 13 items, with 52 as the highest possible score. A higher score in the fatigue scale corresponds to a lower level of fatigue and indicates better quality of life. RVY-02325 To calculate the FACIT-fatigue score, the response scores on negatively phrased questions are reversed and then the 13 item responses are added. Eleven items with responses have their scores reversed (item score=4−response, if the response is not missing), and two items (items 7-8) have their responses unchanged. All items are added so that higher scores correspond to less fatigue. In cases where individual questions are skipped, scores are prorated using the average of other answers in the scale. FACIT-Fatigue=13*[sum(reversed items)+sum(items 7-8)] / number of answered items In some embodiments, the effectiveness of nuclease agents of the disclosure or pharmaceutical compositions thereof is demonstrated by assessing an improvement in fatigue in patients treated with a nuclease agent or pharmaceutical composition thereof. In some embodiments, after treatment, fatigue is generally reduced in the patient as measured by the FACIT fatigue scale. In some embodiments, after treatment, fatigue is generally reduced in the patient as measured by the FACIT fatigue scale when compared to the level of fatigue in the patient prior to treatment, and / or when compared to a patient treated with a control formulation. Improvement in fatigue can be evaluated by the minimal clinically important difference (MCID). The MCID for the FACIT-F scale is generally a 6-point improvement in FACIT-F score (Lai, J. S. et al., The Journal of rheumatology, 38(4), 672–679). In some embodiments, there is a minimal clinically important improvement (MCII) in fatigue in the subject after treatment with a nuclease agent of the disclosure as measured by the FACIT fatigue scale. In some embodiments, after treatment, fatigue is reduced by at least 6 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 6 to 30 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 5 to 52 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 10 to 25 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 5 to 52 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 10 to 25 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by 5 to 52 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by 10 to 25 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 5 points in the patient as measured by RVY-02325 FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 10 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 15 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 20 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 25 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 30 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 35 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 40 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 45 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 50 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 52 points in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 100% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 90% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 80% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 80% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 75% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 75% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 50% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 50% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 40% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 40% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 5% to at least 30% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 30% in the patient as measured by FACIT fatigue. In some RVY-02325 embodiments, after treatment, fatigue is reduced by at least 5% to at least 20% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 20% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 10% to at least 15% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 5% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 10% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 15% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 20% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 25% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 30% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 40% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 50% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 60% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 70% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 80% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 90% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 99% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by at least 100% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 5% to about 100% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 10% to about 90% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 5% to about 80% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 10% to about 80% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 5% to about 75% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 10% to about 75% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is RVY-02325 reduced by about 5% to about 50% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 10% to about 50% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 5% to about 40% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 10% to about 40% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 5% to about 30% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 10% to about 30% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 5% to about 20% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 10% to about 20% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 10% to about 15% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 5% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 10% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 15% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 20% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 25% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 30% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 40% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 50% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 60% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 70% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 80% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 90% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 99% in the patient as measured by FACIT fatigue. In some embodiments, after treatment, fatigue is reduced by about 100% in the patient as measured by FACIT fatigue. RVY-02325 In some embodiments, the subject experienced moderate or severe fatigue at screening as determined by a FACIT fatigue scale. In some embodiments, the subject had a FACIT-fatigue score of less than 20-40 at screening as determined by a FACIT fatigue scale. In some embodiments, the subject had a FACIT-fatigue score of less than 40 at screening as determined by a FACIT fatigue scale. In some embodiments, the subject had a FACIT-fatigue score of less than 35 at screening as determined by a FACIT fatigue scale. In some embodiments, the subject had a FACIT-fatigue score of less than 30 at screening as determined by a FACIT fatigue scale. In some embodiments, the subject had a FACIT-fatigue score of less than 25 at screening as determined by a FACIT fatigue scale. In some embodiments, the subject had a FACIT-fatigue score of less than 20 at screening as determined by a FACIT fatigue scale. In some embodiments, the patient has a SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) viral infection. In some embodiments, the patient has symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the patient has fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the disclosure provides that the FACIT fatigue scale can be used to measure fatigue in patients with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is reduced in a patient treated with a nuclease agent as measured by the FACIT fatigue scale. In some embodiments, fatigue associated with a SARS- CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is reduced in a patient treated with a nuclease agent as measured by the FACIT fatigue scale when compared to the level of fatigue in the patient prior to treatment. In some embodiments, fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is reduced in a patient treated with a nuclease agent as measured by the FACIT fatigue scale when compared to the level of fatigue in a patient treated with a control formulation. Profile of Fatigue The Profile of Fatigue (ProF) is an assessment tool for characterizing fatigue. The words patients use to express their complaints of fatigue, discomfort, and pain are used in the ProF questionnaire. Previously, the ProF has been shown to be a reliable and valid instrument for measuring the severity of fatigue and general discomfort in patients with primary Sjogren’s RVY-02325 syndrome. In some embodiments, the disclosure provides that ProF can be used to measure the severity of fatigue in patients with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. The ProF is a 16-item self-administered questionnaire divided into two domains, one for somatic fatigue and one for mental fatigue. The somatic fatigue domain includes 12 items divided into four facets: (a) need rest (four items), (b) poor starting (three items), (c) low stamina (three items), and (d) weak muscles (two items). The mental fatigue domain includes 4 items is divided into two facets: (a) poor concentration (two items) and (b) poor memory (two items). Patient’s score each item on a scale of 0-7 (0 = ‘no problem at all’ and 7 = “as bad as imaginable’) based on how the patient felt at their worst over the past two weeks. The score for each facet can be obtained by adding up the item scores within each facet and dividing the sum by the number of items in each facet. The score for each domain (e.g., somatic, mental) can be obtained by adding up the facet scores within each domain and dividing the sum by the number of facets within each domain. Higher scores indicate greater fatigue. (Bowman et al., Rheumatology, 2004; 43: 758-764; Strombeck et al., Scand. J. Rheumatol.2005;34:455-459; Segal et al., Arthritis Rheum. 2008 Dec.15; 59(12):1780-1787). In some embodiments, the effectiveness of nuclease of the disclosure, or pharmaceutical compositions thereof is demonstrated by assessing an improvement in fatigue in patients treated with a nuclease agent of the disclosure, or pharmaceutical composition thereof. In some embodiments, after treatment, fatigue is generally reduced in the patient as measured by ProF. In some embodiments, after treatment, fatigue is generally reduced in the patient as measured by ProF when compared to the level of fatigue in the patient prior to treatment, and / or when compared to a patient treated with a control formulation. In some embodiments, there is a minimal clinically important improvement in fatigue in the subject after treatment with a nuclease agent of the disclosure as measured by ProF. In some embodiments, the patient has a SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) viral infection. In some embodiments, the patient has symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the patient has fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the disclosure provides that ProF can be used to measure fatigue in patients with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. RVY-02325 In some embodiments, fatigue associated with a SARS-CoV viral infection is reduced in a patient treated with a nuclease agent as measured by ProF. In some embodiments, fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is reduced in a patient treated with a nuclease agent as measured by the ProF when compared to the level of fatigue in the patient prior to treatment. In some embodiments, fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is reduced in a patient treated with a nuclease agent as measured by ProF when compared to the level of fatigue in a patient treated with a control formulation. Assessing a Reduction in SARS-CoV virus infection Associated Fatigue In some embodiments, the effectiveness of a nuclease agent of the disclosure is demonstrated by assessing a reduction of fatigue in patients treated with a nuclease agent of the disclosure. In some embodiments, a patient treated with a nuclease agent of the disclosure will demonstrate a reduction in fatigue when compared to the level of fatigue in the patient prior to treatment, and / or when compared to a patient treated with a control formulation. In some embodiments, fatigue is associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the patient’s condition is evaluated by measuring fatigue in the patient by one or more patient reported indices (e.g., PROF, FACIT, PROMIS, PGA) as compared to the level of fatigue in the patient prior to treatment or relative to the levels of fatigue in a similarly afflicted untreated or control patient. In some embodiments, the effectiveness of a nuclease agent is demonstrated by assessing the Profile or Fatigue (PROF), Physician Global Assessment (PGA), Patient Reported Outcome Measurement Information System (PROMIS), and / or the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale in patients treated with a nuclease agent disclosed herein when compared to patients treated with control formulations. In some embodiments, a patient treated with a nuclease agent will demonstrate an improvement in the PROF, PGA, PROMIS, and / or the FACIT fatigue scale when compared to the patient’s, PROF, PGA, PROMIS, and / or the FACIT fatigue scale prior to the treatment, or when compared to a patient treated with a control formulation. For example, a human subject in need of treatment is selected or identified. The subject can be in need of, e.g., treating a cause or symptom of SARS-CoV (e.g., SARS-CoV-1 and / or RVY-02325 SARS-CoV-2) virus infection, such as fatigue. The identification of the subject can occur in a clinical setting, or elsewhere, e.g., in the subject's home through the subject's own use of a self- testing kit. In some embodiments, at baseline (day 1), a suitable first dose of a nuclease agent is administered to the subject. The nuclease agent is formulated as described herein. In some embodiments, the patient’s condition is evaluated at baseline (day 1) and after a period of time following the first dose, e.g., day 8, day 15, day 29, day 43, day 57, day 71, day 85, day 99 or at the end of the study, e.g., by PROMIS, PGA, PROF and / or the FACIT fatigue scale. Other relevant criteria can also be measured. The number and strength of doses are adjusted according to the subject's needs. In some embodiments, a dose of about 5-10mg / kg of the nuclease agent of the disclosure is administered to the subject. In some embodiments, a dose of about 3-10mg / kg of the nuclease agent of the disclosure is administered to the subject. In some embodiments, a dose of about 10mg / kg of the nuclease agent of the disclosure is administered to the subject. In some embodiments, a dose of at least 10mg / kg of the nuclease agent of the disclosure is administered to the subject. In some embodiments, the nuclease agent of the disclosure is administered to the subject weekly. In some embodiments, at least two doses of the nuclease agent are administered to the subject. In some embodiments, at least three doses of the nuclease agent are administered to the subject. In some embodiments, at least four doses of the nuclease agent are administered to the subject. In some embodiments, at least five doses of the nuclease agent are administered to the subject. In some embodiments, at least six doses of the nuclease agent are administered to the subject. In some embodiments, the nuclease agent are administered to the subject so long as fatigue improves. After treatment, an improvement in one or more of the following outcomes can be noted: (1) an improvement in PROF, or an improvement in the PROF relative to the PROF prior to treatment, or relative to a similarly afflicted but untreated / control subject, (2) an improvement in the FACIT fatigue scale, or an improvement can be noted in the FACIT fatigue scale relative to the FACIT fatigue scale prior to treatment, or relative to a similarly afflicted but untreated / control subject, (3) an improvement in the PROMIS scale, or an improvement can be noted in the PROMIS scale relative to the PROMIS scale prior to treatment, or relative to a similarly afflicted but untreated / control subject, (4) an improvement in the PGA scale, or an improvement can be noted in the PGA scale relative to the PGA fatigue scale prior to treatment, or relative to a similarly afflicted but untreated / control subject.. RVY-02325 Neuropsychological Analysis of Fatigue Assays Various neuropsychological assays known in the art can be used to assess the efficacy of nuclease agents of the disclosure. Digit Symbol Substitution Test The Digit Symbol Substitution Test (DSST) provides a valid and sensitive test to measure cognitive dysfunction that is impacted by many domains. The DSST is sensitive to both the presence of cognitive dysfunction as well as a change in cognitive function across a range of clinical populations. This neuropsychological test is widely used, highly validated, and extremely sensitive test reading out on executive function related inputs. In some embodiments, the disclosure provides that DSST can be used to measure the severity of cognitive dysfunction in patients with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. DSST is a time limited paper-and-pencil cognitive test that is given on a single sheet of paper. The test requires a patient to match symbols to numbers according to a key at the top of the paper. The patient copies the symbol into spaces below a row of numbers and the number of correct symbols within the allowed time (e.g., 90 or 120 seconds) is calculated. The test provides data on the accuracy and rate of performing the task. A patient’s performance on the DSST correlates with real-world functional outcomes, such as the ability to accomplish everyday tasks, and recovery from functional disability in a range of psychiatric conditions. The DSST test can be used to assess attention and / or focus in the patient. DSST is a polyfactorial test that measures a range of cognitive operations and provides a practical and effective method to monitor cognitive function over time. To perform well on the DSST the patient must have intact motor speed, attention and visuoperceptual functions, including scanning and the ability to write or draw (i.e., basic mental dexterity). DSST offers high sensitivity to detect cognitive impairment and has many benefits including brevity, reliability, sensitivity to change, and minimal impact on language, culture and education on test performance. (Jaeger, J., Journal of Clinical Psycopharmacology, 38(5), 513-518, October 2018). Furthermore, DSST is used in clinical development to define pharmacokinetic / pharmacodynamic (PK / PD) relationship. This test is also used as a PD RVY-02325 biomarker in CNS studies and can discriminate between two doses of selective serotonin reuptake inhibitors (SSRI). In some embodiments, the effectiveness of a nuclease agent of the disclosure or pharmaceutical composition thereof is demonstrated by assessing an improvement in cognitive function in patients treated with a nuclease agent of the disclosure or pharmaceutical composition thereof. After treatment, cognitive function is generally improved in the patient as measured by the DSST test when compared to the level of cognitive function in the patient prior to treatment, and / or when compared to a patient treated with a control formulation. In some embodiments, the patient has a SARS-CoV (e.g., SARS-CoV-1 and / or SARS- CoV-2) viral infection. In some embodiments, the patient has symptoms associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the patient has fatigue associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the disclosure provides that DSST can be used to measure cognitive function in patients with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, reduced cognitive function associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is improved in a patient treated with a nuclease agent of the disclosure as measured by DSST. In some embodiments, reduced cognitive function associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is improved in a patient treated with a nuclease agent as measured by the DSST when compared to the level of cognitive function in the patient prior to treatment. In some embodiments, reduced cognitive function associated with a SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) viral infection is improved in a patient treated with a nuclease agent as measured by DSST when compared to the level of cognitive function in a patient treated with a control formulation. Assessing Improvement in SARS-CoV Virus Infection Associated Cognitive Function In some embodiments, the effectiveness of a nuclease agent of the disclosure is demonstrated by assessing an improvement in cognitive function in patients treated with a nuclease agent of the disclosure. In some embodiments, a patient treated with a nuclease agent of the disclosure demonstrates an improvement in cognitive function when compared to the level of cognitive function in the patient prior to treatment, and / or when compared to a patient treated RVY-02325 with a control formulation. In some embodiments, the patient has a SARS-CoV (e.g., SARS- CoV-1 and / or SARS-CoV-2) viral infection. In some embodiments, the patient’s condition is evaluated by measuring cognitive function in the patient by one or more neuropsychological assays (e.g., DSST) as compared to the level of cognitive function in the patient prior to treatment or relative to the level of cognitive function in a similarly afflicted untreated or control patient. In some embodiments, the effectiveness of a nuclease agent of the disclosure is demonstrated by assessing the results of a DSST test in patients treated with a nuclease agent disclosed herein when compared to patients treated with control formulations. In some embodiments, a patient treated with a nuclease agent of the disclosure will demonstrate an improvement in the DSST test when compared to the patient’s DSST test score prior to the treatment, or when compared to a patient treated with a control formulation. For example, a human subject in need of treatment is selected or identified. The subject can be in need of, e.g., treating a cause or symptom of SARS-CoV (e.g., SARS-CoV-1 and / or SARS-CoV-2) virus infection, such as cognitive dysfunction. The identification of the subject can occur in a clinical setting, or elsewhere, e.g., in the subject's home through the subject's own use of a self-testing kit. At baseline (day 1), a suitable first dose of a nuclease agent of the disclosure is administered to the subject. The nuclease agent is formulated as described herein. The patient’s condition is evaluated at baseline (day 1) and after a period of time following the first dose, e.g., day 8, day 15, day 29, day 43, day 57, day 71, day 85, day 99 or at the end of the study, e.g., by DSST. Other relevant criteria can also be measured. The number and strength of doses are adjusted according to the subject's needs. After treatment, an improvement in the DSST test score relative to the DSST test score prior to treatment, or relative to a similarly afflicted but untreated / control subject. Nuclease Agents RNase In some embodiments, the nuclease agents of the disclosure, including RNase-Fc fusion proteins, include at least one enzymatically active RNase domain, or fragment or variant thereof, such as a human RNase 1, or fragment or variant thereof, operably linked to a PK moiety which RVY-02325 provides a scaffold and / or extends the in vivo half-life of the RNase domain as compared to a nuclease domain without such a PK moiety. In some embodiments, the nuclease agents include at least one enzymatically active RNase domain, or fragment or variant thereof, such as a human RNase 1, or fragment or variant thereof, operably linked to an Fc domain, such as a human IgG1 Fc domain, or a variant or fragment thereof, that alters the serum half-life of the nuclease molecule to which it is fused compared to nuclease molecules that are not fused to the Fc domain, or a variant or fragment thereof. In some embodiments, the nuclease agents of the disclosure, include at least one RNase domain, or variant or fragment thereof, operably coupled to an Fc domain, or a variant or fragment thereof, via a linker domain. In some embodiments, the linker domain is a linker peptide. In some embodiments, the linker domain is a linker nucleotide. In some embodiments, the nuclease agents of the disclosure include a leader sequence, e.g., a leader peptide. In some embodiments, the leader molecule is a leader peptide positioned at the N-terminus of the nuclease domain. In some embodiments, a nuclease agent comprises a leader peptide at the N-terminus of the molecule, wherein the leader peptide is later cleaved from the nuclease agent. Methods for generating nucleic acid sequences encoding a leader peptide fused to a recombinant protein are well known in the art. In some embodiments, the nuclease agents are expressed either with or without a leader fused to their N-terminus. The protein sequence of nuclease agent of the present disclosure following cleavage of a fused leader peptide can be predicted and / or deduced by one of skill in the art. In some embodiments the leader is a VK3 leader peptide (VK3LP), wherein the leader peptide is fused to the N-terminus of the nuclease agent. Such leader sequences can improve the level of synthesis and secretion of the nuclease agent in mammalian cells. In some embodiments, the leader is cleaved, yielding nuclease agents. In some embodiments, a nuclease agent of the present disclosure is expressed without a leader peptide fused to its N-terminus, and the resulting nuclease agent has an N-terminal methionine. In some embodiments, the nuclease agents of the disclosure include a VK3 leader peptide fused to the N-terminus of the nuclease agent, e.g., SEQ ID NO: 49 (RSLV-132). In some embodiments, the nuclease agents of the disclosure do not include a leader sequence, e.g., SEQ ID NO: 50 (RSLV-132). RVY-02325 In some embodiments, a nuclease agent includes an RNase domain operably coupled to the N- or C-terminus of an Fc domain, or a variant or fragment thereof. In some embodiments, the nuclease agent comprises both an RNase domain and a DNase domain, In some embodiments, the nuclease agent includes two nuclease domains (e.g., two RNase domains) operably coupled to each other in tandem and further operably coupled to the N- or C-terminus of the same or different Fc domains, or a variant or fragment thereof. In some embodiments, the nuclease agent includes a mammalian RNase 1. In some embodiments, the nuclease agent includes a primate RNase 1. In some embodiments, the nuclease agent includes a rodent RNase 1. In some embodiments, the nuclease agent includes a mouse RNase 1. In some embodiments, the nuclease agent includes a rat RNase 1. In some embodiments, the nuclease agent includes a monkey RNase 1. In some embodiments, the nuclease agent includes a goat RNase 1. In some embodiments, the nuclease agent includes a rabbit RNase 1. In some embodiments, the nuclease agent includes a horse RNase 1. In some embodiments, the nuclease agent includes a canine RNase 1. In some embodiments, the RNase 1 domain is a mutant RNase 1 domain. The Sequence Table provides the sequences of exemplary nuclease agents of various configurations. In some embodiments, a nuclease agent is a multi-nuclease protein (e.g., two RNA nucleases, or an RNase and a DNase) fused to the same or different Fc domains, or a variant or fragment thereof, or other methods of prolonging serum half-life (for example, albumin or PEGylation), that digests RNA molecules specifically bound to circulating immunoglobulins. In one embodiment, the nuclease domain is operably coupled (e.g., chemically conjugated or genetically fused (e.g., either directly or via a polypeptide linker)) to the N- terminus of a Fc domain, or a variant or fragment thereof. In another embodiment, the nuclease domain is operably coupled (e.g., chemically conjugated or genetically fused (e.g., either directly or via a polypeptide linker)) to the C-terminus of a Fc domain, or a variant or fragment thereof. In other embodiments, a nuclease domain is operably coupled (e.g., chemically conjugated or genetically fused (e.g., either directly or via a polypeptide linker)) via an amino acid side chain of a Fc domain, or a variant or fragment thereof. In some embodiments, the nuclease agents of the disclosure comprise two or more nuclease domains and at least one Fc domain, or a variant or fragment thereof. For example, RVY-02325 nuclease domains may be operably coupled to both the N-terminus and C-terminus of the same or different Fc domains, or variants or fragments thereof, with optional linkers between the nuclease domains and the Fc domain(s), variant(s) or fragment(s) thereof. In some embodiments, the nuclease domains are identical, e.g., RNase and RNase. In other embodiments, the nuclease domains are different, e.g., two different RNA nucleases or RNase and DNase. In some embodiments, two or more nuclease domains are operably coupled to each other (e.g., via a polypeptide linker) in series, and the tandem array of nuclease domains is operably coupled (e.g., chemically conjugated or genetically fused (e.g., either directly or via a polypeptide linker)) to either the C-terminus or the N-terminus of the same or different Fc domains, or variants or fragments thereof. In other embodiments, the tandem array of nuclease domains is operably coupled to both the N-terminus and the C-terminus of the same Fc domain, or a variant or fragment thereof. In some embodiments, the nuclease domains are operably linked in tandem (e.g., N- RNase- RNase -C, N-RNase-DNase-C, or N-DNase-RNase-C) with or without a linker to the N-or C- terminus of the same or different Fc domains. In some embodiments, the tandem nuclease proteins form a homodimer or a heterodimer. In other embodiments, one or more nuclease domains are inserted between two Fc domains, or variants or fragments thereof. For example, one or more nuclease domains may form all or part of a polypeptide linker of nuclease agent of the disclosure. In some embodiments, the nuclease agents comprise at least two nuclease domains (e.g., RNase and RNase or RNase and DNase), at least one linker domain, and at least one Fc domain, or a variant or fragment thereof. In some embodiments, the nuclease agents of the disclosure comprise a Fc domain, or a variant or fragment thereof, as described herein, thereby increasing serum half-life and bioavailability of the nuclease agents. In some embodiments, a nuclease agent comprises one or more polypeptides such as a polypeptide comprising an amino acid sequence as shown in any of SEQ ID NOs: 44-58. It will be understood by the skilled artisan that other configurations of the nuclease domains and Fc domains are possible, with the inclusion of optional linkers between the nuclease domains and / or between the nuclease domains and Fc domain. It will also be understood that RVY-02325 domain orientation can be altered, so long as the nuclease domains are active in the particular configuration tested. In some embodiments, the nuclease agents of the disclosure have at least one nuclease domain specific for a target molecule which mediates a biological effect. In some embodiments, binding of the nuclease agents of the disclosure to a target molecule (e.g. RNA or DNA) results in the reduction or elimination of the target molecule, e.g., from a cell, a tissue, or from circulation. In some embodiments, the nuclease agents of the disclosure may be assembled together or with other polypeptides to form binding proteins having two or more polypeptides ("multimers"), wherein at least one polypeptide of the multimer is a nuclease agent of the disclosure. Exemplary multimeric forms include dimeric, trimeric, tetrameric, and hexameric altered binding proteins and the like. In some embodiments, the polypeptides of the multimer are the same (i.e., homomeric altered binding proteins, e.g., homodimers, homotetramers). In some embodiments, the polypeptides of the multimer are different (e.g., heteromeric). In some embodiments, the nuclease agents of the disclosure are assembled together to form a dimer. In some embodiments, the dimer is a homodimer. In some embodiments, the dimer is a heterodimer. In some embodiments, a nuclease agent has a serum half-life that is increased at least about 1.5-fold, such as at least 3-fold, at least 5-fold, at least 10-fold, at least about 20-fold, at least about 50-fold, at least about 100-fold, at least about 200-fold, at least about 300-fold, at least about 400-fold, at least about 500-fold, at least about 600-fold, at least about 700-fold, at least about 800-fold, at least about 900-fold, at least about 1000-fold, or 1000-fold or greater relative to the corresponding nuclease molecules not fused to the Fc domain, or a variant or fragment thereof. In some embodiments, a nuclease agent has a serum half-life that is decreased at least about 1.5-fold, such as at least 3-fold, at least 5-fold, at least 10-fold, at least about 20- fold, at least about 50-fold, at least about 100-fold, at least about 200-fold, at least about 300- fold, at least about 400-fold, at least about 500-fold, or 500-fold or lower relative to the corresponding nuclease molecules not fused to the Fc domain, or a variant or fragment thereof. Routine art-recognized methods can be used to determine the serum half-life of nuclease agents of the disclosure. RVY-02325 In some embodiments, the activity of the RNase in the nuclease agent is not less than about 10-fold less, such as 9-fold less, 8-fold less, 7-fold less, 6-fold less, 5-fold less, 4-fold less, 3-fold less, or 2-fold less than the activity of a control RNase molecule. In some embodiments, the activity of the RNase in the nuclease agent is about equal to the activity of a control RNase molecule. In some embodiments, the nuclease agents can be active towards freely circulating DNA and / or RNA molecules, or DNA and / or RNA molecules complexed with immunoglobulin molecules, (e.g., either in soluble form or deposited as insoluble complexes). In some embodiments, the nuclease agents can be active towards circulating RNA, for example, circulating viral RNA. In some embodiments, the activity of the nuclease agent is detectable in vitro and / or in vivo. In some embodiments, a multifunctional RNase molecule is provided that is attached to another enzyme or antibody having binding specificity, such as an scFv targeted to RNA or DNA or a second nuclease domain with the same or different specificities as the first domain. In some embodiments, linker domains include (gly4ser) 3, 4 or 5 variants that alter the length of the linker by 5 amino acid progressions. In some embodiments, a linker domain is approximately 18 amino acids in length and includes an N-linked glycosylation site, which can be sensitive to protease cleavage in vivo. In some embodiments, an N-linked glycosylation site can protect the nuclease agents from cleavage in the linker domain. In some embodiments, an N- linked glycosylation site can assist in separating the folding of independent functional domains separated by the linker domain. In some embodiments, the linker domain is an NLG linker (VDGASSPVNVSSPSVQDI) (SEQ ID NO: 37). DNase In some embodiments, the nuclease agents include substantially all or at least an enzymatically active fragment of a DNase. In some embodiments, the DNase is a Type I secreted DNase, preferably a human DNase such as mature human pancreatic DNase 1 (UniProtKB entry P24855, SEQ ID NO: 82). In some embodiments, a naturally occurring variant allele, A114F (SEQ ID NO: 77), which shows reduced sensitivity to actin is included in a RVY-02325 DNase1 of an RNase-Fc fusion protein (see Pan et al., JBC 1998;273:18374-81; Zhen et al., BBRC 1997;231:499-504; Rodriguez et al., Genomics 1997;42:507-13). In other embodiments, a naturally occurring variant allele, G105R (SEQ ID NO: 78), which exhibits high DNase activity relative to wild type DNase1, is included in a DNase1 of a nuclease agent (see Yasuda et al., Int J Biochem Cell Biol 2010;42:1216-25). In some embodiments, this mutation is introduced into a nuclease agentto generate a more stable derivative of human DNase1. In some embodiments, the DNase is human, wild type DNase1 or human, DNase1 A114F mutated to remove all potential N-linked glycosylation sites, i.e., asparagine residues at positions 18 and 106 of the DNase1 domain set forth in SEQ ID NO: 82 (i.e., human DNase1 N18S / N106S / A114F, SEQ ID NO: 80), which correspond to asparagine residues at positions 40 and 128, respectively, of full length pancreatic DNase1 with the native leader (SEQ ID NO: 3). In some embodiments, the DNase is a mutated human DNase. In some embodiments, the DNase is a mutated human DNase comprising A114F and G105R mutations. In some embodiments, the DNase is a human DNase1 comprising one or more basic (i.e., positively charged) amino acid substitutions to increase DNase functionality and chromatin cleavage. In some embodiments, basic amino acids are introduced into human DNase1 at the DNA binding interface to enhance binding with negatively charged phosphates on DNA substrates (see US 7407785; US 6391607). This hyperactive DNase1 may be referred to as "chromatin cutter." In some embodiments, 1, 2, 3, 4, 5 or 6 basic amino acid substitutions are introduced into DNase1. For example, one or more of the following residues is mutated to enhance DNA binding: Gln9, Glu13, Thr14, His44, Asn74, Asn110, Thr205. In some embodiments one or more of the foregoing amino acids are substituted with basic amino acids such as, arginine, lysine and / or histidine. For example, a human DNase can include one or more of the following substitutions: Q9R, E13R, T14K, H44K, N74K, N110R, T205K. In some embodiments, the human DNase1 also includes an A114F substitution, which reduces sensitivity to actin (see US 6348343). In one embodiment, the human DNase1 includes the following substitutions: E13R, N74K, A114F and T205K. In some embodiments, the human DNase1 further includes mutations to remove potential glycosylation sites, e.g., asparagine residues at positions 18 and 106 of the DNase1 domain set forth in SEQ ID NO: 82, which correspond to asparagines residues at positions 40 and 128, RVY-02325 respectively of full length pancreatic DNase1 with the native leader. In one embodiment, the human DNase1 includes the following substitutions: E13R / N74K / A114F / T205K / N18S / N106S. In some embodiments, the DNase is DNase 1-like (DNaseL) enzyme, 1-3 (UniProtKB entry Q13609; SEQ ID NO: 5). In some embodiments, the DNase is three prime repair exonuclease 1 (TREX1; UniProtKB entry Q9NSU2; SEQ ID NO: 16). In some embodiments, the DNase is DNase2. In some embodiments, the DNase2 is DNAse2 alpha (i.e., DNase2; UnitProtKB entry O00115 SEQ ID NO: 18) or DNase2 beta (i.e., DNase2-like acid DNase; UnitProtKB entry Q8WZ79; SEQ ID NO: 19). In some embodiments, the N-linked glycosylation sites of DNase 1L3, TREX1, DNase2 alpha, or DNase2 beta are mutated such as to remove potential N-linked glycosylation sites. In some embodiments, a DNase-linker-Fc domain containing a 20 or 25 aa linker domain is made. In some embodiments, the activity of the DNase in the nuclease agent is not less than about 10-fold less, such as 9-fold less, 8-fold less, 7-fold less, 6-fold less, 5-fold less, 4-fold less, 3-fold less, or 2-fold less than the activity of a control DNase molecule. In some embodiments, the activity of the DNase in the nuclease agent is about equal to the activity of a control DNase molecule. In some embodiments, the nuclease of the disclosure includes a human RNase 1. In some embodiments, the nuclease agent includes a wild-type human RNase 1 domain. In some embodiments, the nuclease agent includes human pancreatic RNase1 (UniProtKB entry P07998; SEQ ID NO: 1) of the RNase A family. In some embodiments, the nuclease agent includes the mature form of human pancreatic RNase1 as set forth in SEQ ID NO: 2. In some embodiments, the RNase domain includes a human RNase 1 domain having one or more mutations. In some embodiments, the human RNase1 is mutated to remove all potential N-linked glycosylation sites, i.e., asparagine residues at positions 34, 76, and 88 of the RNase1 domain set forth in SEQ ID NO: 2 (human RNase1 N34S / N76S / N88S, SEQ ID NO: 4), which correspond to asparagine residues at positions 62, 104, and 116, respectively, of full length pancreatic RNase1 with the native leader (SEQ ID NO: 1). In some embodiments, a RNase1-linker-Fc containing a 20 or 25 aa linker domain is made. Nuclease Agents RVY-02325 In some embodiments, a nuclease agents of the disclosure include an RNase molecule attached to an Fc domain that digests RNA molecules specifically bound to circulating immunoglobulins. In some embodiments, the Fc domain does not effectively bind Fc^ receptors. In one aspect, the nuclease agent does not effectively bind C1q. In other aspects, the nuclease agent comprises an in-frame Fc domain from IgG1. In other aspects, the nuclease agent further comprises mutations in the hinge, CH2, and / or CH3 domains. In other aspects, the mutations are P238S, P331S or N297S, and may include mutations in one or more of the three hinge cysteines. In some such aspects, the mutations are in one or more of three hinge cysteines at residues 220, 226, and 229, numbering according to the EU index, such as substitution of one or more cysteine residues with serine, for example, C220S, C226S and / or C229S. In some embodiments, one of three hinge region cysteines are replaced by serine, for example, C220S also referred to herein as “SCC hinge”. In some embodiments, all three hinge region cysteines are replaced by serine, C220S, C226S and C229S, also referred to herein as “SSS hinge”. In other aspects, the nuclease agents contain the SCC hinge, but are otherwise wild type for human IgG1 Fc CH2 and CH3 domains, and bind efficiently to Fc receptors, facilitating uptake of the nuclease agent into the endocytic compartment of cells to which they are bound. In other aspects, the nuclease agent has activity against single and / or double-stranded RNA substrates. In some embodiments, a nuclease agent includes a mutant Fc domain. In some embodiments, a nuclease agent includes a mutant, IgG1 Fc domain. In some embodiments, a mutant Fc domain comprises one or more mutations in the hinge, CH2, and / or CH3 domains. In some embodiments, a mutant Fc domain includes a P238S mutation. In some embodiments, a mutant Fc domain includes a P331S mutation. In some embodiments, a mutant Fc domain includes a P238S mutation and a P331S mutation. In some embodiments, a mutant Fc domain comprises P238S and / or P331S and may include mutations in one or more of the three hinge cysteines. In some embodiments, a mutant Fc domain comprises P238S and / or P331S, and / or one or more mutations in the three hinge cysteines. In some embodiments, a mutant Fc domain comprises P238S and / or P331S, and / or mutations in the three hinge cysteines to SSS or in one hinge cysteine to SCC. In some embodiments, a mutant Fc domain comprises P238S and P331S and mutations in the three hinge cysteines. In some embodiments, a mutant Fc domain comprises P238S and P331S and either SCC or SSS. In some embodiments, a mutant Fc domain comprises P238S and P331S and SCC. In some embodiments, a mutant Fc domain includes RVY-02325 P238S SSS. In some embodiments, a mutant Fc domain includes P331S and either SCC or SSS. In some embodiments, a mutant Fc domain includes mutations in one or more of the three hinge cysteines. In some embodiments, a mutant Fc domain includes mutations in the three hinge cysteines. In some embodiments, a mutant Fc domain includes mutations in the three hinge cysteines to SSS. In some embodiments, a mutant Fc domain includes mutations in one of the three hinge cysteines to SCC. In some embodiments, a mutant Fc domain includes SCC or SSS. In some embodiments, a mutant Fc domain is as shown in any of SEQ ID NOs: 21-28. In some embodiments, a nuclease agent is as shown in any of SEQ ID NOs 44-58. In some embodiments, a nuclease agent comprises a wild-type, human RNase1 domain linked to a mutant, human IgG1 Fc domain comprising SCC, P238S, and P331S, or a mutant, human IgG1 Fc domain comprising SSS, P238S, and P331S. In some embodiments, a nuclease agent is shown in SEQ ID NOs: 45-46. In some embodiments, an RNase-Fc fusion protein is shown in SEQ ID NO: 50. In some embodiments, an RNase-Fc fusion protein comprises a wild-type, human RNase1 domain linked via a (Gly4Ser)4 linker domain to a mutant, human IgG1 Fc domain comprising SCC, P238S, and P331S or a mutant, human IgG1 Fc domain comprising SSS, P238S, and P331S. In some embodiments, an RNase-Fc fusion protein is shown in SEQ ID NOs: 47-48. In some embodiments, a nuclease agent of the disclosure comprises a human DNase1 G105R A114F domain linked via a (Gly4Ser)4 linker domain to a mutant, human IgG1 Fc domain comprising SCC, P238S, and P331S linked via a NLG linker domain to a wild-type, human RNase1 domain. In some embodiments, a nuclease agent comprises a human DNase1 G105R A114F domain linked via a (Gly4Ser)4 linker domain to a mutant, human IgG1 Fc domain comprising SSS, P238S, and P331S linked via a NLG linker domain to a wild-type, human RNase1 domain. In some embodiments, a nuclease agent is shown in SEQ ID NOs: 51- 52. In some embodiments, a nuclease agent comprises a wild-type, human RNase1 domain linked via a (Gly4Ser)4 linker domain to a mutant, human IgG1 Fc domain comprising SCC, P238S, and P331S linked via a NLG linker domain to a human DNase1 G105R A114F domain. In some embodiments, a nuclease agent comprises a wild-type, human RNase1 domain linked via a (Gly4Ser)4 linker domain to a mutant, human IgG1 Fc domain comprising SSS, P238S, and RVY-02325 P331S linked via a NLG linker domain to a human DNase1 G105R A114F domain. In some embodiments, a nuclease agent is shown in SEQ ID NOs: 53-54. In some embodiments, a nuclease agent comprises a wild-type, human RNase1 domain linked to a mutant, human IgG1 Fc domain comprising SCC, P238S, and P331S linked via a NLG linker domain to a human DNase1 G105R A114F domain. In some embodiments, a nuclease agent comprises a wild-type, human RNase1 domain linked to a mutant, human IgG1 Fc domain comprising SSS, P238S, and P331S linked via a NLG linker domain to a human DNase1 G105R A114F domain. In some embodiments, a nuclease agent is shown in SEQ ID NOs: 55-58. In some embodiments, the activity of the nuclease agent is detectable in vitro and / or in vivo. In some embodiments, nuclease agents include an RNase domain and an Fc domain, wherein the RNase1 domain is located at the COOH side of the Fc. In other embodiments, nuclease agents include an RNase domain and an Fc domain, wherein the RNase1 domain is located at the NH2 side of the Fc. In some embodiments, nuclease agents include: RNase-Fc; Fc-RNase; Fc-linker-RNase; RNase-linker-Fc, RNase-Fc-DNase; DNase-Fc-RNase; RNase- linker-Fc-linker-DNase; DNase-linker-Fc-linker-RNase; RNase-Fc-linker-DNase; DNase-Fc- linker-RNase; RNase-linker-Fc-DNase; DNase-linker-Fc-RNase. Fc Domains In some embodiments, the polypeptide comprising one or more nuclease domains, or variant or fragment thereof is operably coupled, with or without a linker domain, to a Fc domain, which serves as a scaffold as well as a means to increase the serum half-life of the polypeptide. In some embodiments, the one or more nuclease domains and / or the Fc domain is aglycosylated, deglycosylated, or underglycosylated. In some embodiments, the Fc domain is a mutant or variant Fc domain, or a fragment of an Fc domain. Suitable Fc domains are well-known in the art and include, but are not limited to, Fc and Fc variants, such as those disclosed in WO2011 / 053982, WO 02 / 060955, WO 02 / 096948, WO05 / 047327, WO05 / 018572, and US 2007 / 0111281 (the contents of the foregoing are incorporated herein by reference). It is within the abilities of the skilled artisan to use routine RVY-02325 methods to introduce Fc domains (e.g., cloning, conjugation) into the nuclease agents disclosed herein (with or without altered glycosylation). In some embodiments, the Fc domain is a wild type human IgG1 Fc, such as is shown in SEQ ID NO: 20. In some embodiments, the Fc domain is a human IgG1 Fc domain having one or more mutations. In some embodiments, the Fc domain is a wild type human IgG4 Fc, such as is shown in SEQ ID NOs: 30-31. In some embodiments, the Fc domain is a human IgG4 Fc domain having one or more mutations. In some embodiments, an Fc domain is altered or modified, e.g., by mutation which results in an amino acid addition, deletion, or substitution. As used herein, the term "Fc domain variant" refers to an Fc domain having at least one amino acid modification, such as an amino acid substitution, as compared to the wild-type Fc from which the Fc domain is derived. For example, wherein the Fc domain is derived from a human IgG1 antibody, a variant comprises at least one amino acid mutation (e.g., substitution) as compared to a wildtype amino acid at the corresponding position of the human IgG1 Fc region. The amino acid substitution(s) of an Fc variant may be located at a position within the Fc domain referred to as corresponding to the position number that that residue would be given in an Fc region in an antibody (numbering according to EU index). In some embodiments, the Fc variant comprises one or more amino acid substitutions at an amino acid position(s) located in a hinge region or portion thereof. In some embodiments, the Fc variant comprises one or more amino acid substitutions at an amino acid position(s) located in a CH2 domain or portion thereof. In some embodiments, the Fc variant comprises one or more amino acid substitutions at an amino acid position(s) located in a CH3 domain or portion thereof. In some embodiments, the Fc variant comprises one or more amino acid substitutions at an amino acid position(s) located in a CH4 domain or portion thereof. In some embodiments, the Fc domain comprises one or more of the following amino acid substitutions: T350V, L351Y, F405A, and Y407V. In some embodiments, the Fc domain comprises one or more of the following amino acid substitutions: T350V, T366L, K392L, and T394W. In some embodiments, the human IgG1 Fc region has a mutation at N83 (i.e., N297 by Kabat numbering), yielding an aglycosylated Fc region (e.g., Fc N83S; SEQ ID NO: 21). In RVY-02325 some embodiments, the human IgG1 Fc domain includes mutations in one or more of the three hinge region cysteines (residues 220, 226, and 229, numbering according to the EU index). In some embodiments, one or more of the three hinge cysteines in the Fc domain can be mutated to SCC (SEQ ID NO: 24) or SSS (SEQ ID NO: 25), where in “S” represents an amino acid substitution of cysteine with serine (wherein CCC refers to the three cysteines present in the wild type hinge domain). Accordingly “SCC” indicates an amino acid substitution to serine of only the first cysteine of the three hinge region cysteines (residues 220, 226, and 229, numbering according to the EU index), whereas “SSS” indicates that all three cysteines in the hinge region are substituted with serine (residues 220, 226, and 229, numbering according to the EU index). In some embodiments, the Fc domain is a human IgG1 Fc domain having one or more mutations. In some embodiments, a mutant Fc domain comprises one or more mutations in the hinge, CH2, and / or CH3 domains. In some embodiments, the Fc domain is a human IgG4 Fc domain having one or more mutations. In some embodiments, mutations in the IgG4 Fc domain include one or more mutations selected from the following group of mutations: F296Y, E356K, R409K, and H345R. In some embodiments, mutations in the IgG4 Fc domain includes one or more mutation selected from the following group of mutations: F296Y, R409K, and K439E. In some embodiments, the nuclease agents disclosed herein include a first polypeptide comprising a mutant IgG4 Fc domain, wherein the Fc domain includes mutations F296Y, E356K, R409K, and H345R, and a second polypeptide comprising a mutant IgG4 Fc domain, wherein the CH3 domain includes mutations F296Y, R409K, and K439E. In some embodiments, a mutant IgG4 Fc domain comprises one or more mutations in the hinge, CH2, and / or CH3 domains. CH2 Substitutions In some embodiments, a mutant Fc domain includes a P238S mutation. In some embodiments, a mutant Fc domain includes a P331S mutation. In some embodiments, a mutant Fc domain includes a P238S mutation and a P331S mutation. In some embodiments, a mutant Fc domain comprises P238S and / or P331S, and may include mutations in one or more of the three hinge cysteines (residues 220, 226, and 229), numbering according to the EU index. In some embodiments, a mutant Fc domain comprises P238S and / or P331S, and / or one or more RVY-02325 mutations in the three hinge cysteines (residues 220, 226, and 229), numbering according to the EU index. In some embodiments, a mutant Fc domain comprises P238S and / or P331S, and / or mutations in a hinge cysteine to SCC or in the three hinge cysteines to SSS. In some embodiments, a mutant Fc domain comprises P238S and P331S and mutations in at least one of the three hinge cysteines. In some embodiments, a mutant Fc domain comprises P238S and P331S and SCC. In some embodiments, a mutant Fc domain comprises P238S and P331S and SSS. In some embodiments, a mutant Fc domain includes P238S and SCC or SSS. In some embodiments, a mutant Fc domain includes P331S and SCC or SSS. (All numbering according to the EU index). In some embodiments, a mutant Fc domain includes a mutation at a site of N-linked glycosylation, such as N297, e.g., a substitution of asparagine for another amino acid such as serine, e.g., N297S. In some embodiments, a mutant Fc domain includes a mutation at a site of N-linked glycosylation, such as N297, e.g., a substitution of asparagine for another amino acid such as serine, e.g., N297S and a mutation in one or more of the three hinge cysteines. In some aspects, a mutant Fc domain includes a mutation at a site of N-linked glycosylation, such as N297, e.g., a substitution of asparagine for another amino acid such as serine, e.g., N297S and mutations in one of the three hinge cysteines to SCC or all three cysteines to SSS. In some aspects, a mutant Fc domain includes a mutation at a site of N-linked glycosylation, such as N297, e.g., a substitution of asparagine for another amino acid such as serine, e.g., N297 and one or more mutations in the CH2 domain which decrease Fc^R binding and / or complement activation, such as mutations at P238 or P331 or both, e.g., P238S or P331S or both P238S and P331S. In some embodiments, such mutant Fc domains can further include a mutation in the hinge region, e.g., SCC or SSS. (All numbering according to the EU index.) In some embodiments, the mutant Fc domain is as shown in the Sequence Table or Sequence Listing herein. CH3 Substitutions In some embodiments, heterodimers are formed by mutations in the CH3 domain of the Fc domain on the heterodimeric nuclease agents disclosed herein. Heavy chains were first engineered for heterodimerization using a "knobs-into-holes" strategy (Rigway B, et al., Protein Eng., 9 (1996) pp.617-621, incorporated herein by reference). The term "knob-into-hole" refers RVY-02325 to the technology directing the pairing of two polypeptides together in vitro or in vivo by introducing a pertuberance (knob) into one polypeptide and a cavity (hole) into the other polypeptide at an interface in which they interact. See e.g., WO 96 / 027011, WO 98 / 050431, US 5,731,168, US2007 / 0178552, WO2009089004, US 20090182127. In particular, a combination of mutations in the CH3 domain can be used to form heterodimers, for example, S354C, T366W in the “knob” heavy chain, and Y349C, T366S, L368A, Y407V in the “hole” heavy chain. In another example, T366Y in the “knob” heavy chain, and Y407T in the “hole” heavy chain. In some embodiments, the heterodimeric nuclease agent disclosed herein includes a first CH3 domain having the knob mutation T366W and a second CH3 domain having the hole mutations T366S, L368A, and Y407V. (Numbering according to the EU index.) In some embodiments, the nuclease agents disclosed herein includes a first CH3 domain having the knob mutation T366Y and a second CH3 domain having the hole mutation Y407T. In some embodiments, the CH3 mutations are those described in US 2012 / 0149876 A1, US 2017 / 0158779, US 9574010, and US 9562109, each of which is incorporated herein by reference; and Von Kreudenstein, T.S. et al. mABs, 5 (2013), pp.646-654, incorporated herein by reference) and include the following mutations: T350V, L351Y, F405A, and Y407V (first CH3 domain); and T350V, T366L, K392L, T394W (second CH3 domain). In some embodiments, the heterodimeric nuclease agents disclosed herein include a first CH3 domain having T350V, L351Y, F405A, and Y407V mutations and a second CH3 domain having T350V, T366L, K392L, T394W mutations. (Numbering according to the EU index.) In some embodiments, heterodimers are formed by mutations in the CH3 domain of the Fc domain on the nuclease agent disclosed herein. In particular, a combination of mutations in the CH3 domain can be used to form heterodimers with high heterodimeric stability and purity; for example, See e.g., Von Kreudenstein et al., mAbs 5:5, 646-654; September-October 2013, and US 2012 / 0149876 A1, US 2017 / 0158779, US 9574010, and US 9562109, each of which is incorporated herein by reference in its entirety. In some embodiments, mutations in the Fc domain include one or more mutations selected from the following group of mutations: T350V, L351Y, F405A, and Y407V. In some embodiments, mutations in the Fc domain include one or more mutation selected from the following group of mutations: T350V, T366L, K392L, and T394W. In some embodiments, the nuclease agent disclosed herein include a CH3 domain having mutations T350V, L351Y, F405A, and Y407V. In some embodiments, the nuclease RVY-02325 agent disclosed herein include a CH3 domain having mutations T350V, T366L, K392L, and T394W. In some embodiments, the nuclease disclosed herein include a first polypeptide comprising a mutant Fc domain, wherein the CH3 domain includes mutations T350V, L351Y, F405A, and Y407V, and a second polypeptide comprising a mutant Fc domain, wherein the CH3 domain includes mutations T350V, T366L, K392L, and T394W. Other mutations in the CH3 domain of the Fc domain are contemplated to preferentially form heterodimers. For example, See e.g., Von Kreudenstein et al., mAbs 5:5, 646-654; September-October 2013, incorporated herein by reference). In some embodiments, mutations in the Fc domain of the first polypeptide include one or more mutations selected from, the following group of mutations: T350V, L351Y, F405A, and Y407V, and mutations in the Fc domain of the second polypeptide include one or more mutations selected from the following group of mutations: T350V, T366L, K392M, and T394W. In some embodiments, mutations in the Fc domain of the first polypeptide include one or more mutations selected from the following group of mutations: L351Y, F405A, and Y407V, mutations in the Fc domain of the second polypeptide include one or more mutations selected from the following group of mutations: T366L, K392M, and T394W. In some embodiments, the CH3 mutations are those described by Moore, G.L. et al. (mABs, 3 (2011), pp.546-557) and include the following mutations: S364H and F405A (first CH3 domain); and Y349T and T394F (second CH3 domain). In some embodiments, the heterodimeric nuclease agent disclosed herein includes a first CH3 domain having S364H and F405A mutations and a second CH3 domain having Y349T and T394F mutations. (Numbering according to the EU index.) In some embodiments, the CH3 mutations are those described by Gunasekaran, K. et al. (J. Biol. Chem., 285 (2010), pp. 19637-19646) and include the following mutations: K409D and K392D (first CH3 domain); and D399K and E365K (second CH3 domain). In some embodiments, the heterodimeric nuclease agent disclosed herein includes a first CH3 domain having K409D and K392D mutations and a second CH3 domain having D399K and E365K mutations. (Numbering according to the EU index.) The nuclease agents of the disclosure may employ art-recognized Fc variants which are known to impart an alteration in effector function and / or FcR binding. For example, a change (e.g., a substitution) at one or more of the amino acid positions disclosed in International PCT RVY-02325 Publications WO88 / 07089A1, WO96 / 14339A1, WO98 / 05787A1, WO98 / 23289A1, WO99 / 51642A1, WO99 / 58572A1, WO00 / 09560A2, WO00 / 32767A1, WO00 / 42072A2, WO02 / 44215A2, WO02 / 060919A2, WO03 / 074569A2, WO04 / 016750A2, WO04 / 029207A2, WO04 / 035752A2, WO04 / 063351 A2, WO04 / 074455A2, WO04 / 099249A2, WO05 / 040217A2, WO04 / 044859, WO05 / 070963A1, WO05 / 077981A2, WO05 / 092925A2, WO05 / 123780A2, WO06 / 019447A1, WO06 / 047350A2, and WO06 / 085967A2; US Patent Publication Nos. US2007 / 0231329, US2007 / 0231329, US2007 / 0237765, US2007 / 0237766, US2007 / 0237767, US2007 / 0243188, US20070248603, US20070286859, US20080057056; or U.S. Pat. Nos. 5,648,260; 5,739,277; 5,834,250; 5,869,046; 6,096,871; 6,121,022; 6,194,551; 6,242,195; 6,277,375; 6,528,624; 6,538,124; 6,737,056; 6,821,505; 6,998,253; 7,083,784; and 7,317,091, each of which is incorporated by reference herein. In one embodiment, the specific change (e.g., the specific substitution of one or more amino acids disclosed in the art) may be made at one or more of the disclosed amino acid positions. In another embodiment, a different change at one or more of the disclosed amino acid positions (e.g., the different substitution of one or more amino acid position disclosed in the art) may be made. Other amino acid mutations in the Fc domain are contemplated to reduce binding to the Fc gamma receptor and Fc gamma receptor subtypes. The assignment of amino acids residue numbers to an Fc domain is in accordance with the definitions of Kabat. See, e.g., Sequences of Proteins of Immunological Interest (Table of Contents, Introduction and Constant Region Sequences sections), 5th edition, Bethesda, MD:NIH vol.1:647-723 (1991); Kabat et al., "Introduction" Sequences of Proteins of Immunological Interest, US Dept of Health and Human Services, NIH, 5th edition, Bethesda, MD vol.1:xiii-xcvi (1991); Chothia & Lesk, J. Mol. Biol. 196:901-917 (1987); Chothia et al., Nature 342:878-883 (1989), each of which is herein incorporated by reference for all purposes.” For example, mutations at positions 238, 239, 248, 249, 252, 254, 255, 256, 258, 265, 267, 268, 269, 270, 272, 279, 280, 283, 285, 298, 289, 290, 292, 293, 294, 295, 296, 298, 301, 303, 305, 307, 312, 315, 322, 324, 327, 329, 330, 331, 333, 334, 335, 337, 338, 340, 356, 360, 373, 376, 378, 379, 382, 388, 389, 398, 414, 416, 419, 430, 434, 435, 437, 438 or 439 of the Fc region can alter binding as described in U.S. Pat. No. 6,737,056, issued May 18, 2004, incorporated herein by reference in its entirety. This patent reported that changing Pro331 in IgG3 to Ser resulted in six fold lower affinity as compared to unmutated IgG3, indicating the RVY-02325 involvement of Pro331 in Fc gamma RI binding. In addition, amino acid modifications at positions 234, 235, 236, and 237, 297, 318, 320 and 322 are disclosed as potentially altering receptor binding affinity in U.S.5,624,821, issued April 29, 1997 and incorporated herein by reference in its entirety. (Numbering according to the EU index.) Further mutations contemplated for use include, e.g., those described in U.S. Pat. App. Pub. No.2006 / 0235208, published October 19, 2006 and incorporated herein by reference in its entirety. This publications describe Fc variants that exhibit reduced binding to Fc gamma receptors, reduced antibody dependent cell-mediated cytotoxicity, or reduced complement dependent cytotoxicity, that comprise at least one amino acid modification in the Fc region, including 232G, 234G, 234H, 235D, 235G, 235H, 236I, 236N, 236P, 236R, 237K, 237L, 237N, 237P, 238K, 239R, 265G, 267R, 269R, 270H, 297S, 299A, 299I, 299V, 325A, 325L, 327R, 328R, 329K, 330I, 330L, 330N, 330P, 330R, and 331L (numbering is according to the EU index), as well as double mutants 236R / 237K, 236R / 325L, 236R / 328R, 237K / 325L, 237K / 328R, 325L / 328R, 235G / 236R, 267R / 269R, 234G / 235G, 236R / 237K / 325L, 236R / 325L / 328R, 235G / 236R / 237K, and 237K / 325L / 328R. Other mutations contemplated for use as described in this publication include 227G, 234D, 234E, 234G, 234I, 234Y, 235D, 235I, 235S, 236S, 239D, 246H, 255Y, 258H, 260H, 2641, 267D, 267E, 268D, 268E, 272H, 272I, 272R, 281D, 282G, 283H, 284E, 293R, 295E, 304T, 324G, 324I, 327D, 327A, 328A, 328D, 328E, 328F, 328I, 328M, 328N, 328Q, 328T, 328V, 328Y, 330I, 330L, 330Y, 332D, 332E, 335D, an insertion of G between positions 235 and 236, an insertion of A between positions 235 and 236, an insertion of S between positions 235 and 236, an insertion of T between positions 235 and 236, an insertion of N between positions 235 and 236, an insertion of D between positions 235 and 236, an insertion of V between positions 235 and 236, an insertion of L between positions 235 and 236, an insertion of G between positions 235 and 236, an insertion of A between positions 235 and 236, an insertion of S between positions 235 and 236, an insertion of T between positions 235 and 236, an insertion of N between positions 235 and 236, an insertion of D between positions 235 and 236, an insertion of V between positions 235 and 236, an insertion of L between positions 235 and 236, an insertion of G between positions 297 and 298, an insertion of A between positions 297 and 298, an insertion of S between positions 297 and 298, an insertion of D between positions 297 and 298, an insertion of G between positions 326 and 327, an insertion of A between positions 326 and 327, an insertion of T between positions 326 and 327, an RVY-02325 insertion of D between positions 326 and 327, and an insertion of E between positions 326 and 327 (numbering is according to the EU index). Additionally, mutations described in U.S. Pat. App. Pub. No.2006 / 0235208 include 227G / 332E, 234D / 332E, 234E / 332E, 234Y / 332E, 234I / 332E, 234G / 332E, 235I / 332E, 235S / 332E, 235D / 332E, 235E / 332E, 236S / 332E, 236A / 332E, 236S / 332D, 236A / 332D, 239D / 268E, 246H / 332E, 255Y / 332E, 258H / 332E, 260H / 332E, 264I / 332E, 267E / 332E, 267D / 332E, 268D / 332D, 268E / 332D, 268E / 332E, 268D / 332E, 268E / 330Y, 268D / 330Y, 272R / 332E, 272H / 332E, 283H / 332E, 284E / 332E, 293R / 332E, 295E / 332E, 304T / 332E, 324I / 332E, 324G / 332E, 324I / 332D, 324G / 332D, 327D / 332E, 328A / 332E, 328T / 332E, 328V / 332E, 328I / 332E, 328F / 332E, 328Y / 332E, 328M / 332E, 328D / 332E, 328E / 332E, 328N / 332E, 328Q / 332E, 328A / 332D, 328T / 332D, 328V / 332D, 328I / 332D, 328F / 332D, 328Y / 332D, 328M / 332D, 328D / 332D, 328E / 332D, 328N / 332D, 328Q / 332D, 330L / 332E, 330Y / 332E, 330I / 332E, 332D / 330Y, 335D / 332E, 239D / 332E, 239D / 332E / 330Y, 239D / 332E / 330L, 239D / 332E / 330I, 239D / 332E / 268E, 239D / 332E / 268D, 239D / 332E / 327D, 239D / 332E / 284E, 239D / 268E / 330Y, 239D / 332E / 268E / 330Y, 239D / 332E / 327A, 239D / 332E / 268E / 327A, 239D / 332E / 330Y / 327A, 332E / 330Y / 268 E / 327A, 239D / 332E / 268E / 330Y / 327A, Insert G>297-298 / 332E, Insert A>297- 298 / 332E, Insert S>297-298 / 332E, Insert D>297-298 / 332E, Insert G>326-327 / 332E, Insert A>326-327 / 332E, Insert T>326-327 / 332E, Insert D>326-327 / 332E, Insert E>326-327 / 332E, Insert G>235-236 / 332E, Insert A>235-236 / 332E, Insert S>235-236 / 332E, Insert T>235- 236 / 332E, Insert N>235-236 / 332E, Insert D>235-236 / 332E, Insert V>235-236 / 332E, Insert L>235-236 / 332E, Insert G>235-236 / 332D, Insert A>235-236 / 332D, Insert S>235-236 / 332D, Insert T>235-236 / 332D, Insert N>235-236 / 332D, Insert D>235-236 / 332D, Insert V>235- 236 / 332D, and Insert L>235-236 / 332D (numbering according to the EU index) are contemplated for use. The mutant L234A / L235A is described, e.g., in U.S. Pat. App. Pub. No.2003 / 0108548, published June 12, 2003 and incorporated herein by reference in its entirety. In embodiments, the described modifications are included either individually or in combination. (Numbering according to the EU index.) PK moieties In some embodiments, the RNase is operably coupled to a PK moiety, which serves as a scaffold as well as a means to increase the serum half-life of the RNase. RVY-02325 Suitable PK moieties are well-known in the art and include, but are not limited to, albumin, transferrin, Fc, and their variants, and polyethylene glycol (PEG) and its derivatives. Suitable PK moieties include, but are not limited to, HSA, or variants or fragments thereof, such as those disclosed in US 5,876,969, WO 2011 / 124718, and WO 2011 / 0514789; Fc and Fc variants, such as those disclosed in WO2011 / 053982, WO 02 / 060955, WO 02 / 096948, WO05 / 047327, WO05 / 018572, and US 2007 / 0111281; transferrin, or variants or fragments thereof, as disclosed in US 7,176,278 and US 8,158,579; and PEG or derivatives, such as those disclosed in Zalipsky et al. ("Use of Functionalized Poly(Ethylene Glycols) for Modification of Polypeptides" in Polyethylene Glycol Chemistry: Biotechnical and Biomedical Applications, J. M. Harris, Plenus Press, New York (1992)), and in Zalipsky et al. Advanced Drug Reviews 1995:16: 157-182), and US Pat. Nos.4,640,835, 4,496,689, 4,301,144, 4,670,417, 4,791,192, 4,179,337, and 5,932,462 (the contents of the foregoing are incorporated herein by reference). It is within the abilities of the skilled artisan to use routine methods to operably couple PK moieties (e.g., cloning, conjugation) to the RNase of the invention. In some embodiments, the PK moiety is HSA, which is naturally aglycosylated. In some embodiments, the PK moiety is a wild type Fc (SEQ ID NO: 20). In some embodiments, an Fc domain is altered or modified, e.g., by amino acid mutation (e.g., addition, deletion, or substitution). As used herein, the term "Fc domain variant" refers to an Fc domain having at least one amino acid modification, such as an amino acid substitution, as compared to the wild-type Fc from which the Fc domain is derived. For example, wherein the Fc domain is derived from a human IgG1 antibody, a variant comprises at least one amino acid mutation (e.g., substitution) as compared to a wild type amino acid at the corresponding position of the human IgG1 Fc region. For example, wherein the Fc domain is derived from a human IgG4 antibody, a variant comprises at least one amino acid mutation (e.g., substitution) as compared to a wild type amino acid at the corresponding position of the human IgG4 Fc region. In some embodiments, the PK moiety is any of the Fc variants described herein. In some embodiments, the PK moiety is a wild type HST. In other embodiments, the PK moiety is a HST with a mutations at N413 and / or N611 and / or S12 (S12 is a potential O-linked glycosylation site), yielding a HST with altered glycosylation (i.e., HST N413S, HST N611S, HST N413S / N611S and HST S12A / N413S / N611S). RVY-02325 In some embodiments, a nuclease agent of the disclosure comprises a nuclease domain operably linked, with or without a linker, to human serum albumin (HSA). In some embodiments, a nuclease agent of the disclosure comprises a nuclease domain operably linked, with or without a linker, to a glycoprotein. In some embodiments, a nuclease agent of the disclosure comprises a nuclease domain operably linked, with or without a linker, to transferrin. Linker Domains In some embodiments, a nuclease agent includes a linker domain. In some embodiments, a nuclease agent includes a plurality of linker domains. In some embodiments, the linker domain is a polypeptide linker. In certain aspects, it is desirable to employ a polypeptide linker to fuse Fc, or a variant or fragment thereof, with one or more nuclease domains to form a nuclease agent. In one embodiment, the polypeptide linker is synthetic. As used herein, the term "synthetic" with respect to a polypeptide linker includes peptides (or polypeptides) which comprise an amino acid sequence (which may or may not be naturally occurring) that is linked in a linear sequence of amino acids to a sequence (which may or may not be naturally occurring) (e.g., a Fc sequence) to which it is not naturally linked in nature. For example, the polypeptide linker may comprise non-naturally occurring polypeptides which are modified forms of naturally occurring polypeptides (e.g., comprising a mutation such as an addition, substitution or deletion) or which comprise a first amino acid sequence (which may or may not be naturally occurring). The polypeptide linkers of the invention may be employed, for instance, to ensure that Fc, or a variant or fragment thereof, is juxtaposed to ensure proper folding and formation of a functional Fc, or a variant or fragment thereof. Preferably, a polypeptide linker compatible with the instant invention will be relatively non-immunogenic and not inhibit any non-covalent association among monomer subunits of a binding protein. In some embodiments, the nuclease agent employs an NLG linker as set forth in SEQ ID NO: 37. In some embodiments, the nuclease agents of the disclosure employ a polypeptide linker to join any two or more domains in frame in a single polypeptide chain. In one embodiment, the two or more domains may be independently selected from any of the Fc domains, or variants or fragments thereof, or nuclease domains discussed herein. In some embodiments, the RNase RVY-02325 domain of the nuclease agent is operably coupled to the Fc domain via a linker domain. In some embodiments, a polypeptide linker can be used to fuse identical Fc fragments, thereby forming a homodimeric Fc region. In other embodiments, a polypeptide linker can be used to fuse different Fc fragments, thereby forming a heterodimeric Fc region. In other embodiments, a polypeptide linker of the invention can be used to genetically fuse the C-terminus of a first Fc fragment to the N-terminus of a second Fc fragment to form a complete Fc domain. In one embodiment, a polypeptide linker comprises a portion of a Fc domain, or a variant or fragment thereof. For example, in one embodiment, a polypeptide linker can comprise a Fc fragment (e.g., C or N domain), or a different portion of a Fc domain or variant thereof. In another embodiment, a polypeptide linker comprises or consists of a gly-ser linker. As used herein, the term “gly-ser linker” refers to a peptide that consists of glycine and serine residues. An exemplary gly / ser linker comprises an amino acid sequence of the formula (Gly4Ser)n, wherein n is a positive integer (e.g., 1, 2, 3, 4, or 5). A preferred gly / ser linker is (Gly4Ser)4. Another preferred gly / ser linker is (Gly4Ser)3. Another preferred gly / ser linker is (Gly4Ser)5. In some embodiments, the gly-ser linker may be inserted between two other sequences of the polypeptide linker (e.g., any of the polypeptide linker sequences described herein). In other embodiments, a gly-ser linker is attached at one or both ends of another sequence of the polypeptide linker (e.g., any of the polypeptide linker sequences described herein). In yet other embodiments, two or more gly-ser linker are incorporated in series in a polypeptide linker. In other embodiments, a polypeptide linker of the invention comprises a biologically relevant peptide sequence or a sequence portion thereof. For example, a biologically relevant peptide sequence may include, but is not limited to, sequences derived from an anti-rejection or anti-inflammatory peptide. Said anti-rejection or anti-inflammatory peptides may be selected from the group consisting of a cytokine inhibitory peptide, a cell adhesion inhibitory peptide, a thrombin inhibitory peptide, and a platelet inhibitory peptide. In a preferred embodiment, a polypeptide linker comprises a peptide sequence selected from the group consisting of an IL-1 inhibitory or antagonist peptide sequence, an erythropoietin (EPO)-mimetic peptide sequence, a thrombopoietin (TPO)-mimetic peptide sequence, G-CSF mimetic peptide sequence, a TNF- antagonist peptide sequence, an integrin-binding peptide sequence, a selectin antagonist peptide sequence, an anti-pathogenic peptide sequence, a vasoactive intestinal peptide (VIP) mimetic RVY-02325 peptide sequence, a calmodulin antagonist peptide sequence, a mast cell antagonist, a SH3 antagonist peptide sequence, an urokinase receptor (UKR) antagonist peptide sequence, a somatostatin or cortistatin mimetic peptide sequence, and a macrophage and / or T-cell inhibiting peptide sequence. Exemplary peptide sequences, any one of which may be employed as a polypeptide linker, are disclosed in U.S. Pat. No.6,660,843, which is incorporated by reference herein. Other linkers that are suitable for use in nuclease agents are known in the art, for example, the serine-rich linkers disclosed in US 5,525,491, the helix forming peptide linkers (e.g., A(EAAAK)nA (n=2-5)) disclosed in Arai et al., Protein Eng 2001;14:529-32, and the stable linkers disclosed in Chen et al., Mol Pharm 2011;8:457-65, i.e., the dipeptide linker LE, a thrombin-sensitive disulfide cyclopeptide linker, and the alpha-helix forming linker LEA(EAAAK)4ALEA(EAAAK)4ALE (SEQ ID NO: 39). Other exemplary linkers include GS linkers (i.e., (GS)n), GGSG (SEQ ID NO: 40) linkers (i.e., (GGSG)n), GSAT linkers (SEQ ID NO: 41), SEG linkers, and GGS linkers (i.e., (GGSGGS)n), wherein n is a positive integer (e.g., 1, 2, 3, 4, or 5). Other suitable linkers for use in the nuclease agents can be found using publicly available databases, such as the Linker Database (ibi.vu.nl / programs / linkerdbwww). The Linker Database is a database of inter-domain linkers in multi-functional enzymes which serve as potential linkers in novel fusion proteins (see, e.g., George et al., Protein Engineering 2002;15:871-9). It will be understood that variant forms of these exemplary polypeptide linkers can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence encoding a polypeptide linker such that one or more amino acid substitutions, additions or deletions are introduced into the polypeptide linker. Mutations may be introduced by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Polypeptide linkers of the disclosure are at least one amino acid in length and can be of varying lengths. In one embodiment, a polypeptide linker of the invention is from about 1 to about 50 amino acids in length. As used in this context, the term “about” indicates + / - two amino acid residues. Since linker length must be a positive integer, the length of from about 1 to about 50 amino acids in length, means a length of from 1 to 48-52 amino acids in length. In another embodiment, a polypeptide linker of the disclosure is from about 10-20 amino acids in length. In RVY-02325 another embodiment, a polypeptide linker of the disclosure is from about 15 to about 50 amino acids in length. In another embodiment, a polypeptide linker of the disclosure is from about 20 to about 45 amino acids in length. In another embodiment, a polypeptide linker of the disclosure is from about 15 to about 25 amino acids in length. In another embodiment, a polypeptide linker of the disclosure is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 ,57, 58, 59, 60, or 61 or more amino acids in length. Polypeptide linkers can be introduced into polypeptide sequences using techniques known in the art. Modifications can be confirmed by DNA sequence analysis. Plasmid DNA can be used to transform host cells for stable production of the polypeptides produced. Nuclease Agents with Altered Glycosylation Glycosylation (e.g., O-lined or N-linked glycosylation) can impact the serum half-life of the nuclease agents of the disclosure by, e.g., minimizing their removal from circulation by mannose and asialoglycoprotein receptors and other lectin-like receptors. Accordingly, in some embodiments, the nuclease-Fc fusion proteins of the disclosure are prepared in aglycosylated, deglycosylated, or underglycosylated form. Preferably, N-linked glycosylation is altered and the nuclease agent is aglycosyated. In some embodiments, all asparagine residues in a nuclease agent that conform to the Asn-X-Ser / Thr (X can be any other naturally occurring amino acid except Pro) consensus are mutated to residues that do not serve as acceptors of N-linked glycosylation (e.g., serine, glutamine), thereby eliminating glycosylation of the nuclease agent when synthesized in a cell that glycosylates proteins. In some embodiments, nuclease agents lacking N-linked glycosylation sites are produced in mammalian cells. In one embodiment, the mammalian cell is a CHO cell. Accordingly, in a specific embodiment, an aglycosylated nuclease agent is produced in a CHO cell. In other embodiments, a reduction or lack of N-glycosylation is achieved by, e.g., producing nuclease agents in a host (e.g., bacteria such as E. coli), mammalian cells engineered RVY-02325 to lack one or more enzymes important for glycosylation, or mammalian cells treated with agents that prevent glycosylation, such as tunicamycin (an inhibitor of Dol-PP-GlcNAc formation). In some embodiments, the nuclease agents are produced in lower eukaryotes engineered to produce glycoproteins with complex N-glycans, rather than high mannose type sugars (see, e.g., US2007 / 0105127). In some embodiments, glycosylated nuclease agents (e.g., those produced in mammalian cells such as CHO cells) are treated chemically or enzymatically to remove one or more carbohydrate residues (e.g., one or more mannose, fucose, and / or N-acetylglucosamine residues) or to modify or mask one or more carbohydrate residues. Such modifications or masking may reduce binding of the nuclease agents to mannose receptors, and / or asialoglycoprotein receptors, and / or other lectin-like receptors. Chemical deglycosylation can be achieved by treating a nuclease agent with trifluoromethane sulfonic acid (TFMS), as disclosed in, e.g., Sojar et al., JBC 1989;264:2552-9 and Sojar et al., Methods Enzymol 1987;138:341-50, or by treating with hydrogen fluoride, as disclosed in Sojar et al. (1987, supra). Enzymatic removal of N-linked carbohydrates from nuclease-Fc fusion proteins can be achieved by treating a nuclease agent with protein N-glycosidase (PNGase) A or F, as disclosed in Thotakura et al. (Methods Enzymol 1987;138:350-9). Other art-recognized commercially available deglycosylating enzymes that are suitable for use include endo-alpha-N-acetyl-galactosaminidase, endoglycosidase F1, endoglycosidase F2, endoglycosidase F3, and endoglycosidase H. In some embodiments, one or more of these enzymes can be used to deglycosylate the nuclease agents of the disclosure. Alternative methods for deglycosylation are disclosed in, e.g., US 8,198,063. In some embodiments, the nuclease agents are partially deglycosylated. Partial deglycosylation can be achieved by treating the nuclease agents with an endoglycosidase (e.g., endoglycosidase H), which cleaves N-linked high mannose carbohydrate but not complex type carbohydrates, leaving a single GlcNAc residue linked to the asparagine. Nuclease agents treated with endoglycosidase H will lack high mannose carbohydrates, resulting in a reduced interaction with the hepatic mannose receptor. Although this receptor recognizes terminal GlcNAc, the probability of a productive interaction with the single GlcNAc on the protein surface is not as great as with an intact high mannose structure. In other embodiments, glycosylation of a nuclease agent is modified, e.g., by oxidation, reduction, dehydration, substitution, esterification, alkylation, sialylation, carbon-carbon bond RVY-02325 cleavage, or the like, to reduce clearance of the nuclease agents from blood. In some embodiments, the nuclease agents are treated with periodate and sodium borohydride to modify the carbohydrate structure. Periodate treatment oxidizes vicinal diols, cleaving the carbon- carbon bond and replacing the hydroxyl groups with aldehyde groups; borohydride reduces the aldehydes to hydroxyls. Many sugar residues include vicinal diols and, therefore, are cleaved by this treatment. Prolonged serum half-life with periodate and sodium borohydride is exemplified by the sequential treatment of the lysosomal enzyme ^-glucuronidase with these agents (see, e.g., Houba et al. (1996) Bioconjug Chem 1996:7:606-11; Stahl et al. PNAS 1976;73:4045-9; Achord et al. Pediat. Res 1977;11:816-22; Achord et al. Cell 1978;15:269-78). A method for treatment with periodate and sodium borohydride is disclosed in Hickman et al., BBRC 1974;57:55-61. A method for treatment with periodate and cyanoborohydride, which increases the serum half-life and tissue distribution of ricin, is disclosed in Thorpe et al. Eur J Biochem 1985;147:197-206. In one embodiment, the carbohydrate structures of a nuclease agents can be masked by addition of one or more additional moieties (e.g., carbohydrate groups, phosphate groups, alkyl groups, etc.) that interfere with recognition of the structure by a mannose or asialoglycoprotein receptor or other lectin-like receptors. In some embodiments, one or more potential glycosylation sites are removed by mutation of the nucleic acid encoding the nuclease agent, thereby reducing glycosylation (underglycosylation) of the nuclease agent when synthesized in a cell that glycosylates proteins, e.g., a mammalian cell such as a CHO cell. In some embodiments, it may be desirable to selectively underglycosylate the nuclease domain of the nuclease agent by mutating the potential N-linked glycosylation sites therein if, e.g., the underglycosylated nuclease agent exhibits increased activity or contributes to increased serum half-life. In other embodiments, it may be desirable to underglycosylate portions of the nuclease agent such that regions other than the nuclease domain lack N-glycosylation if, for example, such a modification improves the serum half-life of the nuclease-Fc fusion protein. Alternatively, other amino acids in the vicinity of glycosylation acceptors can be modified, disrupting a recognition motif for glycosylation enzymes without necessarily changing the amino acid that would normally be glycosylated. In some embodiments, glycosylation of a nuclease agent can be altered by introducing glycosylation sites. For example, the amino acid sequence of the nuclease-Fc fusion protein can be modified to introduce the consensus sequence for N-linked glycosylation of Asp-X-Ser / Thr RVY-02325 (X is any amino acid other than proline). Additional N-linked glycosylation sites can be added anywhere throughout the amino acid sequence of the nuclease agent. Preferably, the glycosylation sites are introduced in position in the amino acid sequence that does not substantially reduce the nuclease (e.g., RNase and / or DNase) activity of the nuclease agent. The addition of O-linked glycosylation sites has been reported to alter serum half-life of proteins, such as growth hormone, follicle-stimulating hormone, IGFBP-6, Factor IX, and many others (e.g., as disclosed in Okada et al., Endocr Rev 2011;32:2-342; Weenen et al., J Clin Endocrinol Metab 2004;89:5204-12; Marinaro et al., European Journal of Endocrinology 2000;142:512-6; US 2011 / 0154516). Accordingly, in some embodiments, O-linked glycosylation (on serine / threonine residues) of the nuclease agent is altered. Methods for altering O-linked glycosylation are routine in the art and can be achieved, e.g., by beta- elimination (see, e.g., Huang et al., Rapid Communications in Mass Spectrometry 2002;16:1199- 204; Conrad, Curr Protoc Mol Biol 2001; Chapter 17:Unit17.15A; Fukuda, Curr Protoc Mol Biol 2001;Chapter 17;Unit 17.15B; Zachara et al., Curr Protoc Mol Biol 2011; Unit 17.6; ); by using commercially available kits (e.g., GlycoProfileTM Beta-Elimination Kit, Sigma); or by subjecting nuclease agent protein to treatment with a series of exoglycosidases such as, but not limited to, ^1-4 galactosidase and ^ –N-acetylglucosaminidase, until only Gal ^1-3GalNAc and / or GlcNAc ^1-3GalNAc remains, followed by treatment with, e.g., endo-^-N- acetylgalactosaminidase (i.e., O-glycosidase). Such enzymes are commercially available from, e.g., New England Biolabs. In yet other embodiments, the nuclease agents are altered to introduce O-linked glycosylation in the nuclease agents as disclosed in, e.g., Okada et al. (supra), Weenen et al. (supra), US2008 / 0274958; and US2011 / 0171218. In some embodiments, one or more O-linked glycosylation consensus sites are introduced into the nuclease agents, such as CXXGGT / S-C (SEQ ID NO: 12) (van den Steen et al., In Critical Reviews in Biochemistry and Molecular Biology, Michael Cox, ed., 1998;33:151-208), NST-E / D-A (SEQ ID NO: 13), NITQS (SEQ ID NO: 14), QSTQS (SEQ ID NO: 15), D / E-FT-R / K-V (SEQ ID NO: 32), C-E / D-SN (SEQ ID NO: 33), and GGSC-K / R (SEQ ID NO: 34). Additional O-linked glycosylation sites can be added anywhere throughout the amino acid sequence of the nuclease agents. Preferably, the glycosylation sites are introduced in position in the amino acid sequence that does not substantially reduce the nuclease (e.g., RNase and / or DNase) activity of the nuclease agents. Alternatively, O-linked sugar moieties are introduced by chemically modifying an amino acid in RVY-02325 the nuclease agents as described in, e.g., WO 87 / 05330 and Aplin et al., CRC Crit Rev Biochem 1981;259-306). In some embodiments, both N-linked and O-linked glycosylation sites are introduced into the nuclease agents, preferably in positions in the amino acid sequence that do not substantially reduce the nuclease (e.g., RNase and / or DNase) activity of the nuclease agent. It is well within the abilities of the skilled artisan to introduce, reduce, or eliminate glycosylation (e.g., N-linked or O-linked glycosylation) in a nuclease agent and determine using routine methods in the art whether such modifications in glycosylation status increases or decreases the nuclease activity or serum half-life of the nuclease agent. In some embodiments, the nuclease agent may comprise an altered glycoform (e.g., an underfucosylated or fucose-free glycan). In some embodiments, a nuclease agent with altered glycosylation has a serum half-life that is increased at least about 1.5-fold, such as at least 3-fold, at least 5-fold, at least 10-fold, at least about 20-fold, at least about 50-fold, at least about 100-fold, at least about 200-fold, at least about 300-fold, at least about 400-fold, at least about 500-fold, at least about 600-fold, at least about 700-fold, at least about 800-fold, at least about 900-fold, at least about 1000-fold, or 1000- fold or greater relative to the corresponding glycosylated nuclease agents (e.g., a nuclease agent in which potential N-linked glycosylation sites are not mutated). Routine art-recognized methods can be used to determine the serum half-life of nuclease agents with altered glycosylation status. In some embodiments, a nuclease agent with altered glycosylation (e.g., a aglycosylated, deglycosylated, or underglycosylated nuclease agents) retains at least 50%, such as at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% of the activity of the corresponding glycosylated nuclease agent (e.g., a nuclease agent in which potential N-linked glycosylation sites are not mutated). In some embodiments, altering the glycosylation status of nuclease agents may increase nuclease activity, either by directly increasing enzymatic activity, or by increasing bioavailability (e.g., serum half-life). Accordingly, in some embodiments, the nuclease activity of nuclease agent with altered glycosylation is increased by at least 1.3-fold, such as at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-fold, at least 4-fold, at least 4.5-fold, at least RVY-02325 5-fold, at least 5.5-fold, at least 6-fold, at least 6.5-fold, at least 7-fold, at least 7.5-fold, at least 8-fold, at least 8.5-fold, at least 9-fold, at least 9.5 fold, or 10-fold or greater, relative to the corresponding glycosylated nuclease agnet (e.g., a nuclease agent in which potential N-linked glycosylation sites are not mutated). The skilled artisan can readily determine the glycosylation status of nuclease agents using art-recognized methods. In a preferred embodiment, the glycosylation status is determined using mass spectrometry. In other embodiments, interactions with Concanavalin A (Con A) can be assessed to determine whether a nuclease agent is underglycosylated. An underglycosylated nuclease agent is expected to exhibit reduced binding to Con A-Sepharose when compared to the corresponding glycosylatednuclease agent. SDS-PAGE analysis can also be used to compare the mobility of an underglycosylated protein and corresponding glycosylated protein. The underglycosylated protein is expected to have a greater mobility in SDS-PAGE compared to the glycosylated protein. Other suitable art-recognized methods for analyzing protein glycosylation status are disclosed in, e.g., Roth et al., International Journal of Carbohydrate Chemistry 2012;1- 10. Pharmacokinetics, such as serum half-life, of nuclease agents with different glycosylation status can be assayed using routine methods, e.g., by introducing the nuclease agents in mice, e.g., intravenously, taking blood samples at pre-determined time points, and assaying and comparing levels and / or enzymatic activity of the nuclease-Fc fusion proteins in the samples. Exemplary Nuclease Agents The nuclease agents of the invention are modular, and can be configured to incorporate various individual domains. For example, in one embodiment, the nuclease agent may include the mutant, human DNase1 A114F domain set forth in (SEQ ID NO: 77). In another embodiment, the nuclease agent may include the mutant, human DNase1 N18S / N106S / A114F domain set forth in SEQ ID NO: 80. In another embodiment, the nuclease agent may include the human, wild-type RNase1 domain set forth in SEQ ID NO: 2. In another embodiment, the nuclease agent may include the human, mutant RNase1 N34S / N76S / N88S domain set forth in SEQ ID NO: 4. In another embodiment, the nuclease agent may include the (Gly4Ser)3 linker domain set forth in SEQ ID NO: 6. In another embodiment, the nuclease agent may include the NLG linker set forth in SEQ ID NO: 37. In another embodiment, the nuclease agent may include RVY-02325 a VK3LP leader (SEQ ID NO: 7). It will be understood to the skilled artisan that these individual domains can be operably coupled to each other in any order to form a nuclease agent that is enzymatically active. For example, as detailed in the specific examples below, RNase1 can be operably coupled to an Fc domain. In another example, RNase1 can be operatively coupled to Fc domain via a (Gly4Ser)3 linker domain. In yet another example, DNase1 A114F can be operatively coupled to Fc domain. In yet another example, DNase1 A114F can be operatively coupled to Fc domain via a (Gly4Ser)3 linker domain. Various other configurations are possible, with non-limiting exemplary configurations disclosed herein, in Figures 1A-1D and in the Sequence Table. In some embodiments, a nuclease agent is shown in SEQ ID NO: 50 (e.g., RSLV-132). RSLV-132 is an RNase-Fc fusion protein that has the following configuration and was generated (Fig. 1A). RSLV-132 is a homodimer comprising two polypeptides each having the amino acid sequence set forth as SEQ ID NO: 50. Each polypeptide of the homodimer has the configuration RNase-Fc, wherein a wild-type human RNase 1 domain (SEQ ID NO: 2) is operably coupled without a linker to the N-terminus of a human IgG1 Fc domain comprising SCC hinge and CH2 mutations P238S and P331S (SEQ ID NO:22). In some embodiments, a nuclease-Fc fusion protein comprises a wild-type, human RNase1 domain operably coupled to a mutant Fc domain comprising SCC hinge and CH2 mutations P238S and P331S, or fragment thereof, and a mutated human DNase1 domain operably coupled to the human RNase1, thereby forming a tandem homodimer. In some embodiments, the DNase1 is linked to the RNase1 via a peptide linker, such as an NLG linker disclosed herein. In some embodiments, the RNase1 is operably linked with or without a linker to the N-terminus of the Fc domain. In some embodiments, a nuclease agent comprises a polypeptide having the amino acid sequence set forth in SEQ ID NO: 59 (e.g., RSLV-145). Tandem homodimer RSLV-145 has the configuration DNase-linker-RNase-Fc, wherein a wild- type, human RNase1 domain (SEQ ID NO: 2) is operably coupled without a linker to the N- terminus to a mutant Fc region comprising SCC hinge and CH2 mutations P238S, P331S (SEQ ID NO: 8) and a mutant human DNase1 domain (SEQ ID NO: 9) is operably coupled to the N- terminus of the RNase1 domain via a NLG linker (SEQ ID NO: 37) (Figure 1C). RVY-02325 In other embodiments, one or more nuclease domains may be inserted between two Fc domains, or variants or fragments thereof. For example, one or more nuclease domains may form all or part of a polypeptide linker of a binuclease-Fc fusion protein of the disclosure. In some embodiments, the binuclease-Fc fusion proteins comprise at least two nuclease domains (e.g., RNase and DNase), at least one linker domain, and at least one Fc domain, or a variant or fragment thereof. In some embodiments, a binuclease-Fc fusion protein comprises a first polypeptide sequence set forth in SEQ ID NO: 61 and a second polypeptide sequence set forth in SEQ ID NO: 62 (e.g., RSLV-147). In some embodiments, a binuclease-Fc fusion protein comprises a first polypeptide sequence set forth in SEQ ID NO: 63 and a second polypeptide sequence set forth in SEQ ID NO: 64 (e.g., RSLV-148). In some embodiments, a binuclease-Fc fusion protein comprises a first polypeptide sequence set forth in SEQ ID NO: 65 and a second polypeptide sequence set forth in SEQ ID NO: 66 (e.g., RSLV-149). In some embodiments, a binuclease-Fc fusion protein comprises a first polypeptide sequence set forth in SEQ ID NO: 71 and a second polypeptide sequence set forth in SEQ ID NO: 72 (e.g., RSLV-152). In some embodiments, a binuclease-Fc fusion protein comprises a first polypeptide sequence set forth in SEQ ID NO: 73 and a second polypeptide sequence set forth in SEQ ID NO: 74 (e.g., RSLV-153). In some embodiments, a binuclease-Fc fusion protein is RSLV-153. In some embodiments, a binuclease- Fc fusion protein comprises a polypeptide sequence set forth in SEQ ID NO: 75 (e.g., RSLV- 154). In some embodiments, the RNase1 is operably linked with or without a linker to the C- terminus of the Fc domain. In some embodiments, a nuclease agent is a binuclease-Fc fusion protein that comprises a polypeptide having the amino acid sequence set forth in SEQ ID NO: 60 (e.g., RSLV-146). In some embodiments, the binuclease-Fc fusion protein is homodimeric or heterodimeric. In some embodiments, a nuclease agent is a homodimeric binuclease-Fc fusion protein that comprises a polypeptide having the amino acid sequence set forth in SEQ ID NO: 58 (e.g., RSLV-133). Each polypeptide of the RSLV-133 homodimer has the configuration RNase-Fc- DNase, wherein a wild-type human RNase 1 domain (SEQ ID NO: 2) is operably coupled without a linker to the N-terminus of a human IgG1 Fc domain comprising SCC hinge and CH2 mutations P238S and P331S (SEQ ID NO:22) and a mutant human DNase domain comprising RVY-02325 mutations G105R and A114F (SEQ ID NO: 29) is operably coupled via an NLG linker to the C- terminus of the human IgG1 Fc domain. (Figure 1B) In some embodiments, a nuclease agent is a heterodimeric binuclease-Fc fusion protein comprising mutant human DNase 1 domain operably coupled with or without a linker to a first mutant Fc domain, having SCC hinge, CH2 mutations P238S, P331S, and CH3 mutations T350V, L351Y, F405A and Y407V, or a variant or fragment thereof, and a wild-type human RNase 1 domain operably coupled with or without a linker to a second mutant Fc domain comprising SCC hinge, CH2 mutations P238S and P331S and CH3 mutations T350V, T366L, K392L and T394W, or a fragment thereof. In some embodiments, the DNase1 and RNase 1 are both linked to the N-terminus of their respective Fc domains. In some embodiments, a binuclease-Fc fusion protein is a heterodimer comprising a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 61 and a polypeptide comprising the amino acid sequence set for in SEQ ID NO: 62 (e.g., RSLV-147) (Fig.1D). In some embodiments, a nuclease agent is a heterodimeric binuclease-Fc fusion protein comprising a mutant human DNase 1 domain and wild-type human RNase 1 domain, both operably coupled with or without a linker to a first mutant Fc domain, comprising SCC hinge, CH2 mutations P238S and P331S and CH3 mutations T350V, T366L, K392L and T394W, or a fragment thereof, and a second mutant Fc domain, having mutations T350V, T366L, K392L and T394W, or fragment thereof. In some embodiments, the DNase1 and RNase 1 are linked to the N-terminus and C-terminus, respectively, of the first and second Fc domains. In some embodiments, a binuclease-Fc fusion protein is a heterodimer comprising a polypeptide comprising the sequence set forth in SEQ ID NO: 63 and a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 64 (e.g., RSLV-148) (Fig. 1D). In some embodiments, a nuclease agent is a heterodimeric binuclease-Fc fusion protein comprising a mutant human DNase 1 domain, operably coupled with or without a linker to a mutant Fc domain comprising SCC hinge, CH2 mutations P238S, P331S and CH3 mutations T350V, L351Y, F405A and Y407V, or fragment thereof, and wild-type human RNase 1 domain, operably coupled with or without a linker to a mutant Fc domain comprising SCC hinge, CH2 mutations P238S, P331S and CH3 mutations T350V, T366L, K392L and T394W, or fragment thereof. In some embodiments, the DNase1 is linked to the N-terminus of the Fc domain and the RNase1 is linked to the C-terminus of the Fc domain. In some embodiments, a binuclease-Fc RVY-02325 fusion protein is a heterodimer comprising a polypeptide comprising the sequence set forth in SEQ ID NO: 65 and a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 66 (e.g., RSLV-149) (Fig.1D). In some embodiments, a nuclease agent is a heterodimeric binuclease-Fc fusion protein comprising a mutant human DNase 1 domain operably coupled with or without a linker to a mutant Fc domain comprising SCC hinge, CH2 mutations P238S, P331S and CH3 mutations T350V, L351Y, F405A and Y407V, or fragment thereof, and a wild-type human RNase 1 domain operably coupled with or without a linker to a mutant Fc domain comprising SCC hinge, CH2 mutations P238S, P331S and CH3 mutations T350V, T366L, K392L and T394W, or fragment thereof. In some embodiments, the DNase1 and RNase 1 are both linked to the C- terminus of their respective Fc domains. In some embodiments, a binuclease-Fc fusion protein is a heterodimer comprising a polypeptide comprising the sequence set forth in SEQ ID NO: 67 and a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 68 (e.g., RSLV- 150). In some embodiments, a binuclease-Fc fusion protein is a heterodimer comprising a polypeptide comprising the sequence set forth in SEQ ID NO: 69 and a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 70 (e.g., RSLV-151). In some embodiments, a nuclease agent is a heterodimeric binuclease-Fc fusion protein comprising a mutant human DNase 1 domain and wild-type human RNase 1 domain, both operably coupled with or without a linker to a mutant Fc domain comprising SCC hinge, CH2 mutations P238S, P331S and CH3 mutations T350V, L351Y, F405A and Y407V, or fragment thereof, and a mutant Fc domain comprising SCC hinge, CH2 mutations P238S, P331S and CH3 mutations T350V, T366L, K392L and T394W, or fragment thereof. In some embodiments, the DNase1 and RNase 1 are linked to the C-terminus and N-terminus, respectively, of the Fc domain. In some embodiments, a binuclease-Fc fusion protein is a heterodimer comprising a polypeptide comprising the sequence set forth in SEQ ID NO: 71 and a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 72 (e.g., RSLV-152) (Fig.1D). In some embodiments, a nuclease agent is a heterodimeric binuclease-Fc fusion protein comprising a mutant human DNase 1 domain, operably coupled with or without a linker to a mutant Fc domain comprising SCC hinge, CH2 mutations P238S, P331S and CH3 mutations T350V, L351Y, F405A and Y407V, or fragment thereof, and wild-type human RNase 1 domain, operably coupled with or without a linker to a mutant Fc domain comprising SCC hinge, CH2 RVY-02325 mutations P238S, P331S and CH3 mutations T350V, T366L, K392L and T394W, or fragment thereof. In some embodiments, the DNase1 is linked to the C-terminus of the Fc domain and the RNase1 is linked to the N-terminus of the Fc domain. In some embodiments, a binuclease-Fc fusion protein is a heterodimer comprising a polypeptide comprising the sequence set forth in SEQ ID NO: 73 and a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 74 (e.g., RSLV-153) (Fig.1D). In some embodiments, a nuclease-Fc fusion protein comprises a polypeptide having the amino acid sequence set forth in SEQ ID NO: 59 (e.g., RSLV-145). Tandem homodimer RSLV- 145 has the configuration DNase-linker-RNase-Fc, wherein a wild-type, human RNase1 domain (SEQ ID NO: 2) is operably coupled without a linker to the N-terminus to a mutant Fc region comprising SCC hinge and CH2 mutations P238S, P331S (SEQ ID NO: 8) and a mutant human DNase1 domain (SEQ ID NO: 9) is operably coupled to the N-terminus of the RNase1 domain via a NLG linker (SEQ ID NO: 37) In some embodiments, a binuclease-Fc fusion protein comprising a polypeptide having an amino acid sequence at least 80% identical, such as 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or at least 99.5% identical to an amino acid sequence of any one of SEQ ID NOs: 59-75. In some embodiments, the polypeptide comprises an amino acid sequence set for in any one of SEQ ID NOs: 59-75. In some embodiments, the foregoing nuclease-Fc fusion proteins have a leader sequence. It will be understood by one of ordinary skill that the leader and linker sequences are optional and are not limited to those described in the embodiments above. For example, the RNase and / or DNase domains can be directly fused to the N- and / or C-terminus of Fc, or variant or fragment thereof; the leader domain can be any of those known in the art to be useful for its intended purpose, e.g., to increase protein expression and / or secretion (e.g., a Gaussia luciferase signal peptide (MGVKVLFALICIAVAEA; SEQ ID NO: 10)); the linker can be any linker known in the art, e.g., (Gly4Ser)n, NLG (VDGASSPVNVSSPSVQDI; SEQ ID NO: 37), LE, thrombin- sensitive disulphide cyclopeptide linker, LEA(EAAAK)4ALEA(EAAAK)4 (SEQ ID NO: 11), or an in vivo cleavable disulphide linker, as described herein. It will also be understood that it is within the abilities of a skilled artisan to make the corresponding changes to the amino acid sequences of the binuclease-Fc fusion protein using routine cloning and recombination methods. It will also be understood that the asparagine residues in the nuclease domains (i.e., N34, N76, RVY-02325 and N88 in RNase1, and N18 and N106 in DNase1) can be substituted with an amino acid other than serine (e.g., glutamine), as long as the amino acid does not serve as an acceptor for N-linked glycosylation. Methods of Making Nuclease Agents The nuclease agents of the disclosure largely may be made in transformed or transfected host cells using recombinant DNA techniques. To do so, a recombinant DNA molecule coding for the peptide is prepared. Methods of preparing such DNA molecules are well known in the art. For instance, sequences coding for the peptides could be excised from DNA using suitable restriction enzymes. Alternatively, the DNA molecule could be synthesized using chemical synthesis techniques, such as the phosphoramidate method. Also, a combination of these techniques could be used. The invention also includes a vector capable of expressing the peptides in an appropriate host. The vector comprises the DNA molecule that codes for the peptides operably coupled to appropriate expression control sequences. Methods of affecting this operative linking, either before or after the DNA molecule is inserted into the vector, are well known. Expression control sequences include promoters, activators, enhancers, operators, ribosomal nuclease domains, start signals, stop signals, cap signals, polyadenylation signals, and other signals involved with the control of transcription or translation. The resulting vector having the DNA molecule thereon is used to transform or transfect an appropriate host. This transformation or transfection may be performed using methods well known in the art. Any of a large number of available and well-known host cells may be used in the practice of this invention. The selection of a particular host is dependent upon a number of factors recognized by the art. These include, for example, compatibility with the chosen expression vector, toxicity of the peptides encoded by the DNA molecule, rate of transformation or transfection, ease of recovery of the peptides, expression characteristics, bio-safety and costs. A balance of these factors must be struck with the understanding that not all hosts may be equally effective for the expression of a particular DNA sequence. Within these general guidelines, useful microbial hosts include bacteria (such as E. coli), yeast (such as Saccharomyces) and other RVY-02325 fungi, insects, plants, mammalian (including human) cells in culture, or other hosts known in the art. In some mebodiments, the nuclease agents of the disclosure are produced in CHO cells. Next, the transformed or transfected host is cultured and purified. Host cells may be cultured under conventional fermentation or culture conditions so that the desired compounds are expressed. Such fermentation and culture conditions are well known in the art. Finally, the peptides are purified from culture by methods well known in the art. The compounds may also be made by synthetic methods. For example, solid phase synthesis techniques may be used. Suitable techniques are well known in the art, and include those described in Merrifield (1973), Chem. Polypeptides, pp.335-61 (Katsoyannis and Panayotis eds.); Merrifield (1963), J. Am. Chem. Soc.85: 2149; Davis et al., Biochem Intl 1985;10: 394-414; Stewart and Young (1969), Solid Phase Peptide Synthesis; U.S. Pat. No. 3,941,763; Finn et al. (1976), The Proteins (3rd ed.) 2: 105-253; and Erickson et al. (1976), The Proteins (3rd ed.) 2: 257-527. Solid phase synthesis is the preferred technique of making individual peptides since it is the most cost-effective method of making small peptides. Compounds that contain derivatized peptides or which contain non-peptide groups may be synthesized by well-known organic chemistry techniques. Other methods are of molecule expression / synthesis are generally known in the art to one of ordinary skill. Pharmaceutical Compositions In some embodiments, the nuclease agents of the disclosure (e.g., RNase-Fc fusion proteins, e.g., RSLV-132) are administered alone. In some embodiments, a nuclease agent is administered prior to the administration of at least one other therapeutic agent. In some embodiments, a nuclease agent is administered concurrent with the administration of at least one other therapeutic agent. In some embodiments, a a nuclease agent is administered subsequent to the administration of at least one other therapeutic agent. In other embodiments, a nuclease agent is administered prior to the administration of at least one other therapeutic agent. As will be appreciated by one of skill in the art, in some embodiments, a nuclease agent is combined with the other agent / compound. In some embodiments, a nuclease agent and the other agent are administered concurrently. In some embodiments, the a nuclease agent and the other agent are not administered simultaneously, with the nuclease agent being administered before or after the RVY-02325 other agent is administered. In some embodiments, the subject receives both the nuclease agent and the other agent during a same period of prevention, occurrence of a disorder, and / or period of treatment. Pharmaceutical compositions of the disclosure can be administered in combination therapy, i.e., combined with other agents. In some embodiments, the combination therapy comprises a nuclease agent, in combination with at least one other agent. Agents include, but are not limited to, in vitro synthetically prepared chemical compositions, antibodies, antigen binding regions, and combinations and conjugates thereof. In some embodiments, an agent can act as an agonist, antagonist, allosteric modulator, or toxin. In some embodiments, the disclosure provides for pharmaceutical compositions comprising a nuclease agent (e.g., RNase-Fc fusion proteins, e.g., RSLV-132) together with a pharmaceutically acceptable diluent, carrier, solubilizer, emulsifier, preservative and / or adjuvant. In some embodiments, the disclosure provides for pharmaceutical compositions comprising a nuclease agent and a therapeutically effective amount of at least one additional therapeutic agent, together with a pharmaceutically acceptable diluent, carrier, solubilizer, emulsifier, preservative and / or adjuvant. In some embodiments, acceptable formulation materials preferably are nontoxic to recipients at the dosages and concentrations employed. In some embodiments, the formulation material(s) are for s.c. and / or I.V. administration. In some embodiments, the pharmaceutical composition can contain formulation materials for modifying, maintaining or preserving, for example, the pH, osmolality, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption or penetration of the composition. In some embodiments, suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine or lysine); antimicrobials; antioxidants (such as ascorbic acid, sodium sulfite or sodium hydrogen-sulfite); buffers (such as borate, bicarbonate, Tris-HCl, citrates, phosphates or other organic acids); bulking agents (such as mannitol or glycine); chelating agents (such as ethylenediamine tetraacetic acid (EDTA)); complexing agents (such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin); fillers; monosaccharides; disaccharides; and other carbohydrates (such as glucose, mannose or dextrins); proteins (such as gelatin); coloring, flavoring and diluting agents; emulsifying agents; hydrophilic polymers (such as polyvinylpyrrolidone); low molecular weight polypeptides; salt- RVY-02325 forming counterions (such as sodium); preservatives (such as benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid or hydrogen peroxide); solvents (such as glycerin, propylene glycol or polyethylene glycol); sugar alcohols (such as mannitol or sorbitol); suspending agents; surfactants or wetting agents (such as pluronics, PEG, sorbitan esters, polysorbates such as polysorbate 20, polysorbate 80, triton, tromethamine, lecithin, cholesterol, tyloxapal); stability enhancing agents (such as sucrose or sorbitol); tonicity enhancing agents (such as alkali metal halides, preferably sodium or potassium chloride, mannitol sorbitol); delivery vehicles; diluents; excipients and / or pharmaceutical adjuvants. (Remington's Pharmaceutical Sciences, 18th Edition, A. R. Gennaro, ed., Mack Publishing Company (1995). In some embodiments, the formulation comprises PBS; 20 mM NaOAC, pH 5.2, 50 mM NaCl; and / or 10 mM NAOAC, pH 5.2, 9% Sucrose. In some embodiments, the pharmaceutical compositions of the disclosure are formulated for intravenous administration. In some embodiments, the pharmaceutical compositions of the disclosure are formulated for intravenous injection. In some embodiments, the pharmaceutical compositions of the disclosure are formulated for intravenous infusion. In some embodiments, the pharmaceutical compositions of the disclosure are formulated for subcutaneous injection. In some embodiments, the pharmaceutical compositions of the disclosure are formulated for subcutaneous administration. In some embodiments, a nuclease agent and / or a therapeutic molecule is linked to a half- life extending vehicle known in the art. Such vehicles include, but are not limited to, polyethylene glycol, glycogen (e.g., glycosylation of the nuclease agent), and dextran. Such vehicles are described, e.g., in U.S. application Ser. No. 09 / 428,082, now U.S. Pat. No. 6,660,843 and published PCT Application No. WO 99 / 25044. In some embodiments, the optimal pharmaceutical composition will be determined by one skilled in the art depending upon, for example, the intended route of administration, delivery format and desired dosage. See, for example, Remington's Pharmaceutical Sciences, supra. In some embodiments, such compositions may influence the physical state, stability, rate of in vivo release and rate of in vivo clearance of the fusion proteins of the disclosure. In some embodiments, the primary vehicle or carrier in a pharmaceutical composition can be either aqueous or non-aqueous in nature. For example, in some embodiments, a suitable vehicle or carrier can be water for injection, physiological saline solution or artificial RVY-02325 cerebrospinal fluid, possibly supplemented with other materials common in compositions for parenteral administration. In some embodiments, the saline comprises isotonic phosphate- buffered saline. In some embodiments, pharmaceutical compositions comprise Tris buffer of about pH 7.0-8.5, or acetate buffer of about H 4.0-5.5, which can further include sorbitol or a suitable substitute therefore. In some embodiments, a composition comprising a nuclease agent, with or without at least one additional therapeutic agents, can be prepared for storage by mixing the selected composition having the desired degree of purity with optional formulation agents (Remington's Pharmaceutical Sciences, supra) in the form of a lyophilized cake or an aqueous solution. Further, in some embodiments, a composition comprising a nuclease agent, with or without at least one additional therapeutic agent, can be formulated as a lyophilizate using appropriate excipients such as sucrose. In some embodiments, the pharmaceutical composition can be selected for parenteral delivery. In some embodiments, the compositions can be selected for inhalation or for delivery through the digestive tract, such as orally. The preparation of such pharmaceutically acceptable compositions is within the ability of one skilled in the art. In some embodiments, the formulation components are present in concentrations that are acceptable to the site of administration. In some embodiments, buffers are used to maintain the composition at physiological pH or at a slightly lower pH, typically within a pH range of from about 5 to about 8. In some embodiments, when parenteral administration is contemplated, a therapeutic composition can be in the form of a pyrogen-free, parenterally acceptable aqueous solution comprising a desired nuclease agent, with or without additional therapeutic agents, in a pharmaceutically acceptable vehicle. In some embodiments, a vehicle for parenteral injection is sterile distilled water in which a nuclease agent, with or without at least one additional therapeutic agent, is formulated as a sterile, isotonic solution, properly preserved. In some embodiments, the preparation can involve the formulation of the desired molecule with an agent, such as injectable microspheres, bio-erodible particles, polymeric compounds (such as polylactic acid or polyglycolic acid), beads or liposomes, that can provide for the controlled or sustained release of the product which can then be delivered via a depot injection. In some embodiments, hyaluronic acid can also be used, and can have the effect of promoting sustained duration in the RVY-02325 circulation. In some embodiments, implantable drug delivery devices can be used to introduce the desired molecule. In some embodiments, a pharmaceutical composition can be formulated for inhalation. In some embodiments, a nuclease agent, with or without at least one additional therapeutic agent, can be formulated as a dry powder for inhalation. In some embodiments, an inhalation solution comprising a nuclease agent, with or without at least one additional therapeutic agent, can be formulated with a propellant for aerosol delivery. In some embodiments, solutions can be nebulized. Pulmonary administration is further described in PCT application no. PCT / US94 / 001875, which describes pulmonary delivery of chemically modified proteins. In some embodiments, it is contemplated that formulations can be administered orally. In some embodiments, a nuclease agent, with or without at least one additional therapeutic agents, that is administered in this fashion can be formulated with or without those carriers customarily used in the compounding of solid dosage forms such as tablets and capsules. In some embodiments, a capsule can be designed to release the active portion of the formulation at the point in the gastrointestinal tract when bioavailability is maximized and pre-systemic degradation is minimized. In some embodiments, at least one additional agent can be included to facilitate absorption of a nuclease agent and / or any additional therapeutic agents. In some embodiments, diluents, flavorings, low melting point waxes, vegetable oils, lubricants, suspending agents, tablet disintegrating agents, and binders can also be employed. In some embodiments, a pharmaceutical composition can involve an effective quantity of a nuclease agent, with or without at least one additional therapeutic agents, in a mixture with non-toxic excipients which are suitable for the manufacture of tablets. In some embodiments, by dissolving the tablets in sterile water, or another appropriate vehicle, solutions can be prepared in unit-dose form. In some embodiments, suitable excipients include, but are not limited to, inert diluents, such as calcium carbonate, sodium carbonate or bicarbonate, lactose, or calcium phosphate; or binding agents, such as starch, gelatin, or acacia; or lubricating agents such as magnesium stearate, stearic acid, or talc. Additional pharmaceutical compositions will be evident to those skilled in the art, including formulations involving a nuclease agent, with or without at least one additional therapeutic agent(s), in sustained- or controlled-delivery formulations. In some embodiments, techniques for formulating a variety of other sustained- or controlled-delivery means, such as RVY-02325 liposome carriers, bio-erodible microparticles or porous beads and depot injections, are also known to those skilled in the art. See for example, PCT Application No. PCT / US93 / 00829 which describes the controlled release of porous polymeric microparticles for the delivery of pharmaceutical compositions. In some embodiments, sustained-release preparations can include semipermeable polymer matrices in the form of shaped articles, e.g. films, or microcapsules. Sustained release matrices can include polyesters, hydrogels, polylactides (U.S. Pat. No. 3,773,919 and EP 058,481), copolymers of L-glutamic acid and gamma ethyl-L-glutamate (Sidman et al, Biopolymers, 22:547-556 (1983)), poly (2-hydroxyethyl-methacrylate) (Langer et al., J Biomed Mater Res, 15: 167-277 (1981) and Langer, Chem Tech, 12:98-105 (1982)), ethylene vinyl acetate (Langer et al, supra) or poly-D(-)-3-hydroxybutyric acid (EP 133,988). In some embodiments, sustained release compositions can also include liposomes, which can be prepared by any of several methods known in the art. See, e.g., Eppstein et al, PNAS, 82:3688- 3692 (1985); EP 036,676; EP 088,046 and EP 143,949. The pharmaceutical composition to be used for in vivo administration typically is sterile. In some embodiments, this can be accomplished by filtration through sterile filtration membranes. In some embodiments, where the composition is lyophilized, sterilization using this method can be conducted either prior to or following lyophilization and reconstitution. In some embodiments, the composition for parenteral administration can be stored in lyophilized form or in a solution. In some embodiments, parenteral compositions generally are placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle. In some embodiments, once the pharmaceutical composition has been formulated, it can be stored in sterile vials as a solution, suspension, gel, emulsion, solid, or as a dehydrated or lyophilized powder. In some embodiments, such formulations can be stored either in a ready-to- use form or in a form (e.g., lyophilized) that is reconstituted prior to administration. In some embodiments, kits are provided for producing a single-dose administration unit. In some embodiments, the kit can contain both a first container having a dried protein and a second container having an aqueous formulation. In some embodiments, kits containing single and multi-chambered pre-filled syringes (e.g., liquid syringes and lyosyringes) are included. In some embodiments, the effective amount of a pharmaceutical composition comprising a nuclease agent, with or without at least one additional therapeutic agent, to be employed RVY-02325 therapeutically will depend, for example, upon the therapeutic context and objectives. One skilled in the art will appreciate that the appropriate dosage levels for treatment, according to some embodiments, will thus vary depending, in part, upon the molecule delivered, the indication for which a nuclease agent, with or without at least one additional therapeutic agent, is being used, the route of administration, and the size (body weight, body surface or organ size) and / or condition (the age and general health) of the patient. In some embodiments, the clinician can titer the dosage and modify the route of administration to obtain the optimal therapeutic effect. In some embodiments, a typical dosage can range from about 0.5 mg / kg to up to about 50 mg / kg or more, depending on the factors mentioned above. In some embodiments, the dosage can range from about 5-10 mg / kg, about 2-8 mg / kg, about 3-6 mg / kg, about 3 mg / kg, about 5 mg / kg, or about 10 mg / kg. In some embodiments, the dosage ranges from about 3-10 mg / kg. In some embodiments, the dosage ranges from about 5-10 mg / kg. In some embodiments, the dose is about 10mg / kg. In some embodiments, the dose...

Claims

RVY-02325 CLAIMS 1. A method for treating one or more symptoms associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, the method comprising administering an effective amount of a composition comprising a nuclease agent to the subject, thereby treating the one or more symptoms in the subject.

2. The method of claim 1, wherein SARS-CoV is SARS-CoV-2.

3. The method of claim 1, wherein SARS-CoV is SARS-CoV-1.

4. The method of claim 1, wherein the infection is an acute infection.

5. The method of claim 1, wherein the infection is a prior infection.

6. The method of any one of the preceding claims, wherein the symptom is fatigue.

7. The method of any one of claims 1-5, wherein the symptom is inflammation.

8. The method of any one of the preceding claims, wherein the symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC).

9. The method of any one of the preceding claims, wherein treatment reduces serum ferritin levels.

10. The method of any one of the preceding claims, wherein treatment reduces serum c- reactive protein (CRP) levels in the subject.

11. The method of any one of the preceding claims, wherein treatment reduces anti- phospholipid IgG in the subject.RVY-02325 12. A method for treating fatigue associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, the method comprising administering an a first dose of a composition comprising a nuclease agent to the subject and at least one subsequent dose to the subject, and wherein the nuclease agent is administered to the subject at an amount of about 5-10 mg / kg, thereby treating fatigue in the subject.

13. The method of any one of the preceding claims, wherein treatment reduces fatigue in the subject according to the Patient Reported Outcome Measurement Information System (PROMIS) SF 7a.

14. The method of any one of the preceding claims, wherein treatment reduces fatigue in the subject by a minimal clinically important improvement (MCII) in a PROMIS score.

15. The method of any one of the preceding claims, wherein treatment reduces fatigue in the subject by at least 0.5 standard deviation in the subject as measured by a PROMIS score.

16. The method of any one of the preceding claims, wherein treatment reduces fatigue in the subject by at least 1 standard deviation in the subject as measured by a PROMIS score.

17. The method of any one of the preceding claims, wherein treatment reduces fatigue in the subject by at least 1.5 standard deviation in the subject as measured by a PROMIS score.

18. The method of any one of the preceding claims, wherein treatment reduces fatigue in the subject by at least 10-15% on the PROMIS score.

19. The method of any one of claims 13-18, wherein the PROMIS score is evaluated prior to treatment and after at least 2 doses of the nuclease agent have been administered to the subject.RVY-02325 20. The method of any one of claims 13-18, wherein the PROMIS score is evaluated prior to treatment and after at least 3 doses of the nuclease agent have been administered to the subject.

21. The method of any one of claims 13-18, wherein the PROMIS score is evaluated prior to treatment and after at least 4 doses of the nuclease agent have been administered to the subject.

22. The method of any one of claims 1-12, wherein treatment reduces fatigue in the subject according to the Physicians Global Assessment (PGA).

23. The method of any one of claims 1-12, wherein treatment reduces fatigue in the subject by a minimal clinically important improvement (MCII) on a PGA score.

24. The method of any one of claims 1-12, wherein treatment reduces fatigue in the subject by at least 10-15% on the PGA score.

25. The method of any one of claims 22-24, wherein the PGA score is evaluated prior to treatment and after at least two doses of the nuclease agent have been administered to the subject.

26. The method of any one of claims 22-24, wherein the PGA score is evaluated prior to treatment and after at least 3 doses of the nuclease agent have been administered to the subject.

27. The method of any one of claims 22-24, wherein the PGA score is evaluated prior to treatment and after at least 4 doses of the nuclease agent have been administered to the subject.

28. The method of any one of claims 1-12, wherein treatment reduces fatigue in the subject according to the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale.

29. The method of any one of claims 1-12, wherein treatment reduces fatigue in the subject by a minimal clinically important improvement (MCII) on a Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale.RVY-02325 30. The method of any one of claims 1-12, wherein treatment reduces fatigue in the subject by at least 10-15% on the FACIT fatigue scale.

31. The method of any one of claims 1-12, wherein treatment reduces fatigue in the subject by at least a 6-point improvement on the FACIT fatigue scale.

32. The method of any one of claims 28-31, wherein the FACIT fatigue score is evaluated prior to treatment and after at least two doses of the nuclease agent have been administered to the subject.

33. The method of any one of claims 28-31, wherein the FACIT fatigue score is evaluated prior to treatment and after at least 3 doses of the nuclease agent have been administered to the subject.

34. The method of any one of claims 28-31, wherein the FACIT fatigue score is evaluated prior to treatment and after at least 4 doses of the nuclease agent have been administered to the subject.

35. A method for reducing inflammation associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, the method comprising administering a first dose of a composition comprising a nuclease agent to the subject and at least one subsequent dose to the subject, and wherein the nuclease agent is administered to the subject at an amount of about 5-10 mg / kg, thereby reducing inflammation in the subject.

36. The method of any one of claims 1-12 or 35, wherein the method reduces serum ferritin levels.

37. The method of any one of claims 1-12 or 35, wherein the method reduces serum ferritin levels by at least 10-15%.RVY-02325 38. The method of any one of claims 1-12 or 35, wherein the method reduces serum ferritin levels by at least 10%.

39. The method of any one of claims 1-12 or 35, wherein the method reduces serum ferritin levels by at least 15%.

40. The method of any one of claims 1-12 or 35, wherein the method reduces serum c- reactive protein (CRP) levels in the subject.

41. The method of any one of claims 1-12 or 35, wherein the method reduces serum c- reactive protein (CRP) levels in the subject by at least 10-15%.

42. The method of any one of claims 1-12 or 35, wherein the method reduces serum c- reactive protein (CRP) levels in the subject by at least 10%.

43. The method of any one of claims 1-12 or 35, wherein the method reduces serum c- reactive protein (CRP) levels in the subject by at least 15%.

44. The method of any one of the preceding claims, wherein the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 1 month to about 2 years prior to treatment.

45. The method of claim 44, wherein the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 6 months prior to treatment.

46. The method of claim 44, wherein the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 1 month to about 3 months prior to treatment.RVY-02325 47. The method of claim 44, wherein the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 3 months to about 6 months prior to treatment.

48. The method of claim 44, wherein the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 6 months to about 9 months prior to treatment.

49. The method of claim 44, wherein the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 9 months to about 12 months prior to treatment.

50. The method of claim 44, wherein the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 6 months to about 12 months prior to treatment.

51. The method of claim 44, wherein the subject experienced symptoms are associated with post-acute sequelae of SARS-CoV-2 infection (PASC) for about 1 year to about 3 years prior to treatment.

52. The method of any one of the preceding claims, wherein the subject is a human subject.

53. The method of any one of the preceding claims, wherein the subject is a female subject.

54. The method of any one of the preceding claims, wherein the subject is positive for anti- nuclear antibodies (ANA).

55. The method of any one of the preceding claims, wherein the subject is positive for anti- nuclear antibodies (ANA) prior to treatment.RVY-02325 56. The method of any one of the preceding claims, wherein the nuclease agent is administered at a dose of about 10mg / kg.

57. The method of any one of the preceding claims, wherein the nuclease agent is administered to the subject via intravenous administration.

58. The method of any one of the preceding claims, wherein the nuclease agent is administered to the subject via subcutaneous administration.

59. The method of any one of claims 1-58, wherein at least 2 doses of the nuclease agent are administered to the subject.

60. The method of any one of claims 1-58, wherein at least 3 doses of the nuclease agent are administered to the subject.

61. The method of any one of claims 1-58, wherein at least 4 doses of the nuclease agent are administered to the subject.

62. The method of any one of claims 1-58, wherein at least 5 doses of the nuclease agent are administered to the subject.

63. The method of any one of claims 1-58, wherein at least 6 doses of the nuclease agent are administered to the subject.

64. The method of any one of claims 1-63, wherein the nuclease agent is administered to the subject once weekly.

65. The method of any one of claims 1-63, wherein the nuclease agent is administered to the subject once monthly.RVY-02325 66. The method of any one of claims 1-63, wherein the nuclease agent is administered to the subject every two weeks.

67. The method of any one of claims 1-63, wherein the nuclease agent is administered to the subject twice monthly.

68. The method of any one of claims 1-58, wherein at least 2 doses of the nuclease agent are administered to the subject once weekly.

69. The method of any one of claims 1-58, wherein at least 3 doses of the nuclease agent are administered to the subject once weekly.

70. The method of any one of claims 1-58, wherein at least 4 doses of the nuclease agent are administered to the subject once weekly.

71. The method of any one of claims 1-58, wherein at least 5 doses of the nuclease agent are administered to the subject once weekly.

72. The method of any one of claims 1-58, wherein at least 6 doses of the nuclease agent are administered to the subject once weekly.

73. The method of any one of claims 1-58, wherein the nuclease agent is administered to the subject once weekly to achieve or maintain a therapeutic effect.

74. The method of any one of claims 1-58, wherein the nuclease agent is administered to the subject twice monthly to achieve or maintain a therapeutic effect.

75. The method of any one of claims 1-58, wherein the nuclease agent is administered to the patient every week for two weeks, and then one administration every two weeks to achieve or maintain a therapeutic effect.RVY-02325 76. The method of any one of claims 1-58, wherein the nuclease agent is administered to the patient every week for three weeks, and then one administration every two weeks to achieve or maintain a therapeutic effect.

77. The method of any one of claims 1-76, wherein the subject experienced moderate or severe fatigue at screening as determined by PROMIS SF 7a.

78. The method of any one of claims 1-76, wherein the subject experienced fatigue at least 0.5 standard deviations above normal at screening as determined by PROMIS SF 7a.

79. The method of any one of claims 1-76, wherein the subject experienced fatigue at least 1 standard deviations above normal at screening as determined by PROMIS SF 7a.

80. The method of any one of claims 1-76, wherein the subject experienced fatigue at least 1.5 standard deviations above normal at screening as determined by PROMIS SF 7a.

81. The method of any one of claims 1-76, wherein the subject experienced moderate or severe fatigue at screening as determined PGA.

82. The method of any one of claims 1-76, wherein the subject experienced fatigue at least 1- 15% above normal at screening as determined PGA.

83. The method of any one of claims 1-76, wherein the subject experienced moderate or severe fatigue at screening as determined by a FACIT fatigue scale.

84. The method of any one of claims 1-76, wherein the subject had a FACIT-fatigue score of less than 20-40 at screening as determined by a FACIT fatigue scale.

85. The method of any one of claims 1-76, wherein the subject had a FACIT-fatigue score of less than 40 at screening as determined by a FACIT fatigue scale.RVY-02325 86. The method of any one of claims 1-76, wherein the subject had a FACIT-fatigue score of less than 35 at screening as determined by a FACIT fatigue scale.

87. The method of any one of claims 1-76, wherein the subject had a FACIT-fatigue score of less than 30 at screening as determined by a FACIT fatigue scale.

88. The method of any one of claims 1-76, wherein the subject had a FACIT-fatigue score of less than 25 at screening as determined by a FACIT fatigue scale.

89. The method of any one of claims 1-76, wherein the subject had a FACIT-fatigue score of less than 20 at screening as determined by a FACIT fatigue scale.

90. The method of any one of the preceding claims, wherein the nuclease agent comprises an RNase domain and an Fc domain.

91. The method of claim 90, wherein the RNase domain comprises a human pancreatic RNase 1.

92. The method of claim 91, wherein the human pancreatic RNase 1 comprises the amino acid sequence as set forth in SEQ ID NO:

2.

93. The method of any one of the preceding claims, wherein the nuclease agent comprises a wild-type human IgG1 Fc domain or a human IgG1 Fc domain comprising one or more mutations.

94. The method of any one of the preceding claims, wherein the nuclease agent comprises an RNase domain operably linked, with or without a linker domain, to an Fc domain.

95. The method of claim 94, wherein the RNase domain is operably linked, with or without a linker domain, to the N-terminus of the Fc domain.RVY-02325 96. The method of claim 94, wherein the RNase domain is operably linked, with or without a linker domain, to the C-terminus of the Fc domain.

97. The method of any one of claims 90-96, wherein the nuclease agent further comprises a DNase domain.

98. The method of claim 97, wherein the DNase domain is a mutant human DNase domain.

99. The method of claim 98, wherein the mutant human DNase domain comprises a G105R mutation and an A114F mutation.

100. The method of any one of claims 98-99, wherein the mutant human DNase domain comprises the amino acid sequence set forth as SEQ ID NO: 29, or a nuclease agent comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:

29.

101. The method of any one of claims 97-100, wherein the nuclease agent comprises an RNase domain operably linked, with or without a linker domain, to the N- or C- terminus of an Fc domain and a DNase domain operably linked, with or without a linker domain, to the N- or C- terminus of the Fc domain.

102. The method of any one of claims 93-101, wherein the Fc domain comprising one or more mutations has decreased binding to Fc^ receptors on human cells.

103. The method of any one of the preceding claims, wherein the nuclease agent has a reduced effector function optionally selected from the group consisting of opsonization, phagocytosis, complement dependent cytotoxicity, and antibody-dependent cellular cytotoxicity.

104. The method of any one of the preceding claims, wherein the nuclease agent comprises a human IgG1 Fc domain comprising a P238S mutation and a P331S mutation according to EU numbering.RVY-02325 105. The method of any one of the preceding claims, wherein the nuclease agent comprises a human IgG1 Fc domain comprising a hinge domain, a CH2 domain and a CH3 domain.

106. The method of any one of the preceding claims, wherein the nuclease agent comprises a human IgG1 Fc domain comprising a substitution of one or more of three hinge region cysteine residues with serine.

107. The method of any one of the preceding claims, wherein the nuclease agent comprises an Fc domain comprising an SCC mutation (residues 220, 226, and 229), numbering according to the EU index.

108. The method of any one of the preceding claims, wherein the nuclease agent comprises a human IgG1 Fc domain comprising the amino acid sequence as set forth in SEQ ID NO:

22.

109. The method of any one of claims 1-108, wherein the nuclease agent comprises an amino acid sequence as set forth in SEQ ID NO: 50, or a nuclease agent comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:

50.

110. The method of any one of the preceding claims, wherein the nuclease agent is a dimeric nuclease agent.

111. The method of claim 110, wherein the dimeric nuclease agent is a homodimer.

112. The method of any one of claims 1-89, wherein the nuclease agent comprises a first nuclease domain, a second nuclease domain, and an Fc domain, wherein the first nuclease domain is DNase1 and the second nuclease domain is RNase1, wherein the DNase1 is operably linked with or without a linker in tandem from N- to C- terminus to the RNase1, and the Rnase1 is operably linked with or without a linker to the Fc domain.RVY-02325 113. The method of claim 112, wherein the RNase 1 is operably linked to the N-terminus of the Fc domain without a linker.

114. The method of claim 112, wherein the RNase 1 is operably linked to the C-terminus of the Fc domain without a linker.

115. The method of any one of claims 112-114, wherein the DNase 1 is operably linked to the RNase 1 via a linker.

116. The method of any one of claims 112-115, wherein the RNase is a wild type human RNase 1, or a mutant RNase, such as an aglycosylated, underglycosylated, or deglycosylated RNase 1, such as human RNase 1 N34S / N76S / N88S.

117. The method of claim 116, wherein the RNase is wild type human RNase 1.

118. The method of any one of claims 112-117, wherein the DNase is a wild type human DNase 1, or a mutant human DNase 1 A114F, or aglycosylated, underglycosylated, or deglycosylated mutant human DNase1 N18S / N106S / A114F.

119. The method of any one of claims 112-118, wherein the Fc domain comprises a hinge domain, a CH2 domain, and a CH3 domain.

120. The method of claim 119, wherein the Fc domain comprises a substitution in one or more of three hinge region cysteine residues with serine.

121. The method of claim 120, wherein the Fc domain comprises a mutation selected from the group consisting of SCC, SSS (residues 220, 226, and 229), G236R, L328R, L234A, and L235A, numbering according to the EU index.

122. The method of claim 121, wherein the Fc domain comprises an SCC mutation (residues 220, 226, and 229), numbering according to the EU index.RVY-02325 123. The method of any one of claims 112-122, wherein the Fc domain comprises a P238S and a P331S mutation, numbering according to the EU index.

124. The method of any one of claims 112-123, wherein the linker domain is a polypeptide linker, such as a gly-ser linker or an NLG linker (vdgasspvnvsspsvqdi).

125. The method of any one of claims 1-89, wherein the nuclease agent comprises an amino acid sequence set forth in SEQ ID NO: 59 or SEQ ID NO: 60, or a nuclease agent comprising an amino acid se sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 59 or SEQ ID NO:

60.

126. The method of any one of claims 112-125, wherein the nuclease agent is a dimeric nuclease agent.

127. The method of claim 126, wherein the dimeric nuclease agent is a homodimer.

128. The method of any one of claims 1-89, wherein the nuclease agent comprises a heterodimer comprising a first nuclease domain, a second nuclease domain, a first Fc domain and a second Fc domain, wherein the first nuclease domain is DNasel and the second nuclease domain is RNasel, wherein the DNasel is operably linked with or without a linker to the N- or C- terminus of the first Fc domain, and the RNasel is operably linked with or without a linker to the N- or C- terminus of the second Fc domain.

129. The method of claim 128, wherein the DNase 1 is operably linked without a linker to the N-terminus of the first Fc domain and the RNase l is operably linked without a linker to the N- terminus of the second Fc domain.

130. The method of claim128, wherein the DNase 1 is operably linked with a linker to the N- terminus of the first Fc domain and the RNase l is operably linked with a linker to the N- terminus of the second Fc domain.RVY-02325 131. The method of claim 128, wherein the DNase 1 is operably linked with a linker to the N- terminus of the first Fc domain and the RNase l is operably linked without a linker to the C - terminus of the second Fc domain.

132. The method of claim 128, wherein the DNase 1 is operably linked without a linker to the N-terminus of the first Fc domain and the Rnase l is operably linked without a linker to the C- terminus of the second Fc domain.

133. The method of claim 128, wherein the DNase 1 is operably linked with a linker to the N- terminus of the first Fc domain and the RNase l is operably linked with a linker to the C-terminus of the second Fc domain.

134. The method of claim 128 wherein the DNase 1 is operably linked with a linker to the C- terminus of the first Fc domain and the RNase l is operably linked with a linker to the C-terminus of the second Fc domain.

135. The method of claim 128, wherein the DNase 1 is operably linked without a linker to the C- terminus of the first Fc domain and the RNase l is operably linked without a linker to the C- terminus of the second Fc domain.

136. The method of claim 128, wherein the DNase 1 is operably linked with a linker to the C- terminus of the first Fc domain and the RNase l is operably linked without a linker to the N- terminus of the second Fc domain.

137. The method of claim 128, wherein the DNase 1 is operably linked with a linker to the C- terminus of the first Fc domain and the RNase l is operably linked with a linker to the N- terminus of the second Fc domain.RVY-02325 138. The method of any one of claims 128-137, wherein the RNase is a wild type human RNase l, or a mutant RNase, such as an aglycosylated, underglycosylated, or deglycosylated RNase 1, such as human RNase l N34S / N76S / N88S.

139. The method of claim 138, wherein the RNase is wild type human RNase l.

140. The method of any one of claims 128-139, wherein the DNase is a wild type human DNase l, or a mutant human DNase l A114F, or an aglycosylated, underglycosylated, or deglycosylated mutant human DNase l N18S / N106S / A114F.

141. The method of any of claims 128-140, wherein the first and second Fc domains comprise a hinge domain, a CH2 domain and a CH3 domain.

142. The method of claim 141, wherein the first and second Fc domains comprise a substitution of one or more of three hinge region cysteine residues with serine.

143. The method of claim 142, wherein the first and second Fc domains comprise a mutation selected from the group consisting of SCC, SSS (residues 220, 226, and 229), G236R, L328R, L234A, and L235A, numbering according to the EU index.

144. The method of claim 143, wherein the first and second Fc domains comprise an SCC mutation (residues 220, 226, and 229), numbering according to the EU index.

145. The method of any one of claims 128-144, wherein the first and second Fc domains comprise a P238S and a P331 mutation, numbering according to the EU index.

146. The method of any one of claims 128-145, wherein the first and second Fc domains comprise one or more CH3 mutations to preferentially form heterodimers.RVY-02325 147. The method of claim 146, wherein the first Fc domain comprises CH3 mutations T350V, L351Y, F405A, and Y407V, and the second Fc domain comprises CH3 mutations T350V, T366L, K392L, T394W, numbering according to the EU index.

148. The method of any one of claims 128-147, wherein the linker domain is a polypeptide linker, such as a gly-ser linker or an NLG linker (vdgasspvnvsspsvqdi).

149. The method of any one of claims 1-89, wherein the nuclease agent comprises a heterodimer comprising a first and second polypeptide sequence selected from the group consisting of: (i) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 61, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:61; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 62, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 62, or (ii) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 65, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:65; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 66, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:66, or (iii) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO:67, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 67; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 68, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 68, or (iv) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 69, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 69; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 70, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 70, orRVY-02325 (v) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 73, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 73; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 74, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:

74.

150. The method of any one of claims 1-89, wherein the nuclease agent comprises a heterodimer comprising a first nuclease domain, a second nuclease domain and a first Fc domain and a second Fc domain, wherein the first nuclease domain is DNase l and the second nuclease domain is RNase l, wherein (i) the DNase l is operably linked with or without a linker to the N-terminus of the first Fc domain, and the RNase l is operably linked with or without a linker to the C- terminus of the first Fc domain, or (ii) the RNase l is operably linked with or without a linker to the N-terminus of the first Fc domain, and the DNase l is operably linked with or without a linker to the C- terminus of the first Fc domain.

151. The method of claim 150, wherein the DNase 1 is operably linked without a linker to the N-terminus of the first Fc domain and the RNase l is operably linked with a linker to the C- terminus of the first Fc domain.

152. The method of claim 150, wherein the DNase 1 is operably linked with a linker to the N- terminus of the first Fc domain and the RNase l is operably linked with a without a linker to the C-terminus of the first Fc domain.

153. The method of claim 150, wherein the RNase 1 is operably linked without a linker to the N-terminus of the first Fc domain and the DNase 1 is operably linked with a linker to the C- terminus of the first Fc domain.RVY-02325 154. The method of claim 150, wherein the RNase 1 is operably linked with a linker to the N- terminus of the first Fc domain and the DNase 1 is operably linked with a linker to the C- terminus of the first Fc domain.

155. The method of any one of claims 150-154, wherein the RNase is a wild type human RNase l, or a mutant RNase, such as an aglycosylated, underglycosylated, or deglycosylated RNase 1, such as human RNase l N34S / N76S / N88S.

156. The method of claim 155, wherein the RNase is wild type human RNase l.

157. The method of any one of claims 150-156, wherein the DNase is a wild type human DNase l, or a mutant human DNase l A114F, or an aglycosylated, underglycosylated, or deglycosylated mutant human DNase l N18S / N106S / A114F.

158. The method of any one of claims 150-157, wherein the first and second Fc domains comprise a hinge domain, a CH2 domain and a CH3 domain.

159. The method of claim 158, wherein the first and second Fc domains comprise a substitution of one or more of three hinge region cysteine residues with serine.

160. The method of claim 159, wherein the first and second Fc domains comprise a mutation selected from the group consisting of SCC, SSS (residues 220, 226, and 229), G236R, L328R, L234A, and L235A, numbering according to the EU index.

161. The method of claim 160, wherein the first and second Fc domains comprise an SCC mutation (residues 220, 226, and 229), numbering according to the EU index.

162. The method of any one of claims 150-161, wherein the first and second Fc domains comprise a P238S and a P331 mutation, numbering according to the EU index.RVY-02325 163. The method of any one of claims 150-162, wherein the first and second Fc domains comprise one or more CH3 mutations to preferentially form heterodimers.

164. The method of claim 163, wherein the first Fc domain comprises CH3 mutations T350V, L351Y, F405A, and Y407V, and the second Fc domain comprises CH3 mutations T350V, T366L, K392L, T394W, numbering according to the EU index.

165. The method of any one of claims 150-164, wherein the linker domain is a polypeptide linker, such as a gly-ser linker or an NLG linker (vdgasspvnvsspsvqdi).

166. The method of any one of claims 1-89, wherein the nuclease agent comprises a heterodimer comprising a first and second polypeptide sequence selected from the group consisting of: (i) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO:63, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:63; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO:64, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:64, or (ii) a first polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 71, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 71; and a second polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 72, or a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:

72.

167. A kit comprising a container comprising an injectable solution and instructions for use in treating one or more symptoms associated with SARS-CoV viral infection or prior SARS-CoV viral infection in a human subject in need thereof, comprising: a composition comprising an effective amount of a nuclease agent; and one or more pharmaceutically acceptable carriers and / or diluents.RVY-02325 168. The kit of claim 167, wherein the nuclease agent comprises an amino acid sequence as set forth in SEQ ID NO:

50.

169. The kit of claim 167 or 168, wherein the nuclease agent is a dimeric nuclease agent.

170. The method of claim 169, wherein the dimeric nuclease agent is a homodimer.

171. The kit of any one of claims 167-170, wherein the composition comprising the nuclease agent is formulated to be administered at a dose of about 5-10mg / kg.

172. The kit of any one of claims 167-171, wherein the injectable solution is formulated to be administered via intravenous administration.

173. The kit of any one of claims 167-171, wherein the injectable solution is formulated to be administered via subcutaneous administration.

174. A nuclease agent for use in treating one or more symptoms associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof.

175. A nuclease agent for use in treating fatigue associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, wherein the nuclease agent is formulated as a composition to be administrable as a first dose and at least one subsequent dose to the subject, and wherein the nuclease agent is formulated to be administrable at an amount of about 5-10 mg / kg.

176. A nuclease agent for use in reducing inflammation associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, wherein the nuclease agent is formulated as a composition to be administrable as a first dose and at least one subsequent dose to the subject, and wherein the nuclease agent is formulated to be administrable at an amount of about 5-10 mg / kg.RVY-02325 177. Use of a nuclease agent in the manufacture of a medicament for treating one or more symptoms associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof.

178. Use of a nuclease agent in the manufacture of a medicament for treating fatigue associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, wherein the nuclease agent is formulated as a composition to be administrable as a first dose and at least one subsequent dose to the subject, and wherein the nuclease agent is formulated to be administrable at an amount of about 5-10 mg / kg.

179. Use of a nuclease agent in the manufacture of a medicament for reducing inflammation associated with a SARS-CoV virus infection or prior SARS-CoV virus infection in a human subject in need thereof, wherein the nuclease agent is formulated as a composition to be administrable as a first dose and at least one subsequent dose to the subject, and wherein the nuclease agent is formulated to be administrable at an amount of about 5-10 mg / kg.

180. The method of any one of claims 1-166, wherein treatment results in an increase or decrease in expression of one or more genes in response to one or more interferon proteins.

181. The method of claim 180, wherein the one or more interferon proteins are alpha interferon proteins.

182. The method of claim 181, wherein the interferon protein is IFN^.

183. The method of claim 180, wherein the one or more interferon proteins are gamma interferon proteins.

184. The method of claim 183, wherein the interferon protein is IFN^.RVY-02325 185. The method of any one of claims 1-166, wherein the subject is female, and wherein treatment results in an increase or decrease in expression of one or more genes in response to one or more interferon proteins.

186. The method of claim 185, wherein the one or more interferon proteins are alpha interferon proteins.

187. The method of claim 186, wherein the interferon protein is IFN^.

188. The method of claim 185, wherein the one or more interferon proteins are gamma interferon proteins.

189. The method of claim 188, wherein the interferon protein is IFN^.

190. The method of any one of claims 1-166, wherein the subject is female and treatment results in a decrease in expression of at least one gene of a Hallmark Interferon Alpha Response gene set relative to expression of the at least one gene in the subject prior to treatment.

191. The method of any one of claims 1-166, wherein the subject is female and treatment results in a decrease in expression of at least one gene selected from NUB1, PARP12, OASL, MOV10, MX1, TRIM14, UBA7, IFI44, DDX60, PSMB8, USP18, BATF2, IFIH1, GBP4, PSME2, C1S, SLC25A28, NCOA7, RSAD2, CMPK2, LY6E, CSF1, LPAR6, IFI44L, EPSTI1, CXCL10, PSME1, OAS1, LAMP3, TRIM26, LAP3, CD74, CNP, or any combination thereof relative to expression of the at least one genes in the female subject prior to treatment.

192. The method of any one of claims 1-166, wherein the subject is female and treatment results in a decrease in expression of at least one gene of a Hallmark Interferon Gamma Response gene set relative to expression of the at least one gene in the female subject prior to treatment.RVY-02325 193. The method of any one of claims 1-166, wherein the subject is female and treatment results in a decrease in expression of at least one gene selected from IFI35, PML, CFB, STAT4, CD86, VAMP5, LCP2, PARP12, OASL, HLA-B, CXCL9, GPR18, APOL6, VAMP8, ISOC1, PFKP, VCAM1, MX1, TRIM14, NCOA3, RAPGEF6, IFI44, DDX60, CMKLR1, BANK1, GCH1, PSMB8, USP18, NFKB1, BATF2, IFIH1, IFIT1, SLAMF7, HLA-A, OAS2, GBP4, IL2RB, PSME2, SERPING1, C1S, CIITA, CD69, SLC25A28, RSAD2, PTPN1, PTGS2, CMPK2, PSMB10, LY6E, NUP93, C1R, IL6, IFI44L, CFH, EPSTI1, IRF8, CXCL10, IDO1, HLA-DMA, PSME1, ARID5B, MTHFD2, ITGB7, IRF5, SAMHD1, TRIM26, OAS3, SOCS3, IL18BP, LAP3, CD74, HLA-DRB1, PSMB2, IRF4, IL10RA, HLA-DQA1, and ST3GAL5, relative to expression of the at least one gene in the female subject prior to treatment.

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