Compounds and methods for modulating acute activation

Abstract

Provided herein are pharmaceutical compositions comprising an oligomeric compound and a pharmaceutically acceptable diluent wherein the pharmaceutical composition is formulated to ameliorate an acute neurotoxicity (e.g., an acute activation) in a subject in need thereof. Also provided herein are pharmaceutical compositions comprising an oligomeric compound and a pharmaceutically acceptable diluent wherein the pharmaceutical composition is formulated to prevent an acute neurotoxicity (e.g., an acute activation) in a subject in need thereof.

Description

[0001] COMPOUNDS AND METHODS FOR MODULATING ACUTE ACTIVATION Cross-Reference to Related Applications This application claims the benefit of priority to US Provisional Application No.63 / 601,681, filed November 21, 2023, which is incorporated by reference herein in its entirety for any purpose. SEQUENCE LISTING The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled FMDL0018SEQ.xml, created on November 19, 2024, which is 3,574 KB in size. The information in the electronic format of the sequence listing is incorporated herein by reference in its entirety. BACKGROUND Antisense oligonucleotides (ASOs) are a class of therapeutics for treating a variety of diseases and disorders including neurodegenerative diseases and neurodevelopmental disorders. When injected into the cerebrospinal fluid, some of the ASOs induce transient or acute neurotoxicity (or neurobehavioral side effects), ranging from reduced motor activity to acute seizure-like phenotypes (Moazami et al., bioRxiv 2021.02.14.431096). Several studies have been conducted to elucidate the mechanism behind such acute neurotoxicity. Innate immune response and N-methyl-D-aspartate receptors (NMDARs) have been ruled out while inotropic glutamate receptor subtype α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) has been implicated in modulating acute neurotoxicity (Jia et al., Molecular Therapy: Nucleic Acids.2022.31:182-196). Dysregulation of calcium homeostasis, both extracellularly and intracellularly, have also been suggested to play a role in contributing to acute neurotoxicity (Jia et al., 2022; Hagedorn, al., Nucleic Acids Therapeutics.2022.32(3): 151-162). Interestingly, one study shows that addition of calcium ions to an ASO solution worsened rather than improved acute neurotoxicity when the ASO solution is injected by i.c.v. administration in mice (Jia al., 2022). Currently, there is a lack of acceptable options for ameliorating or preventing acute neurotoxicity. It is therefore an objective herein to provide pharmaceutical compounds, formulations, and methods for ameliorating or preventing such acute neurotoxicity. SUMMARY Provided herein are pharmaceutical compositions and methods for ameliorating an acute neurotoxicity associated with administration of an oligomeric compound in a subject. The administration may be by direct injection into the cerebrospinal fluid (CSF) of the subject, which may be intrathecal or intracerebroventricular administration. Also provided herein are pharmaceutical compositions and method for ameliorating or preventing development of an acute neurotoxicity associated with administration of an oligomeric compound in a subject, e.g., compared to administration of a typical formulation of an oligomeric compound. In certain embodiments, the formulation of the oligomeric compound ameliorates acute neurotoxicity. In certain embodiments, the formulation of the oligomeric compound decreases the frequency, duration, and / or intensity of an acute neurotoxicity. In certain embodiments, the formulation of the oligomeric compound prevents an acute neurotoxicity. In certain embodiments, the acute neurotoxicity is an acute activation. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a plot of body weight vs. acute activation for nonhuman primates according to Example 21. Figure 2 is a graph of Mg2+binding saturation for oligonucleotide compound 1101657 according to Example 22. DETAILED DESCRIPTION It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive. Herein, the use of the singular includes the plural unless specifically stated otherwise. As used herein, the use of “or” means “and / or” unless stated otherwise. Furthermore, the use of the term “including” as well as other forms, such as “includes” and “included”, is not limiting. Also, terms such as “element” or “component” encompass both elements and components comprising one unit and elements and components that comprise more than one subunit, unless specifically stated otherwise. The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents, or portions of documents, cited in this application, including, but not limited to, patents, patent applications, articles, books, and treatises, are hereby expressly incorporated by reference for the portions of the document discussed herein, as well as in their entirety. DEFINITIONS Unless specific definitions are provided, the nomenclature used in connection with, and the procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well-known and commonly used in the art. Where permitted, all patents, applications, published applications and other publications and other data referred to throughout the disclosure are incorporated by reference herein in their entirety. Unless otherwise indicated, the following terms have the following meanings: As used herein, “2’-deoxynucleoside” means a nucleoside comprising a 2’-H(H) deoxyribosyl sugar moiety. In certain embodiments, a 2’-deoxynucleoside is a 2’-β-D-deoxynucleoside and comprises a 2’-β-D- deoxyribosyl sugar moiety, which has the β-D ribosyl configuration as found in naturally occurring deoxyribonucleic acids (DNA). In certain embodiments, a 2’-deoxynucleoside or a nucleoside comprising an unmodified 2’-deoxyribosyl sugar moiety may comprise a modified nucleobase or may comprise an RNA nucleobase (uracil). As used herein, “2’-MOE” means a 2’-OCH2CH2OCH3group in place of the 2’-OH group of a ribosyl sugar moiety. A “2’-MOE sugar moiety” means a sugar moiety with a 2’-OCH2CH2OCH3group in place of the 2’-OH group of a ribosyl sugar moiety. Unless otherwise indicated, a 2’-MOE sugar moiety is in the β-D configuration. “MOE” means O-methoxyethyl. As used herein, “2’-MOE nucleoside” or “2’- O(CH2)2OCH3nucleoside” means a nucleoside comprising a 2’-MOE sugar moiety (or 2’-OCH2CH2OCH3ribosyl sugar moiety). As used herein, “2’-OMe” means a 2’-OCH3group in place of the 2’-OH group of a ribosyl sugar moiety. A “2’-O-methyl sugar moiety” means a sugar moiety with a 2’-OCH3group in place of the 2’-OH group of a ribosyl sugar moiety. Unless otherwise indicated, a 2’-OMe has the β-D ribosyl stereochemical configuration. As used herein, “2’-OMe nucleoside” means a nucleoside comprising a 2’-OMe sugar moiety. As used herein, “2’-F” means a 2’-fluoro group in place of the 2’-OH group of a furanosyl sugar moiety. A “2’-F sugar moiety” means a sugar moiety with a 2’-F group in place of the 2’-OH group of a furanosyl sugar moiety. Unless otherwise indicated, a 2’-F sugar moiety is in the β-D-ribosyl configuration. As used herein, “2’-F nucleoside” means a nucleoside comprising a 2’-F modified sugar moiety. As used herein, “2’-substituted nucleoside” means a nucleoside comprising a 2’-substituted furanosyl sugar moiety. As used herein, “2’-substituted” in reference to a sugar moiety means a sugar moiety comprising at least one 2'-substituent group other than H or OH. As used herein, “5-methylcytosine” means a cytosine modified with a methyl group attached to the 5 position. A 5-methylcytosine is a modified nucleobase. As used herein, “abasic sugar moiety” means a sugar moiety that is not attached to a nucleobase. Such abasic sugar moieties are sometimes referred to in the art as “abasic nucleosides.” As used herein, “administration” or “administering” means providing a pharmaceutical agent or composition to a subject. As used herein, “ameliorate” in reference to a treatment means improvement in at least one symptom relative to the same symptom in the absence of the treatment. In certain embodiments, amelioration is the reduction in the severity or frequency of a symptom or the delayed onset or slowing of progression in the severity or frequency of a symptom. In certain embodiments, the symptom is muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, or seizures. The progression or severity of indicators may be determined by subjective or objective measures, which are known to those skilled in the art. As used herein, “antisense activity” means any detectable and / or measurable change attributable to the hybridization of an antisense compound to its target nucleic acid. In certain embodiments, antisense activity is a decrease in the amount or expression of a target nucleic acid or protein encoded by such target nucleic acid compared to target nucleic acid levels or target protein levels in the absence of the antisense compound. As used herein, “antisense agent” means an antisense compound and optionally one or more additional features, such as a sense compound. As used herein, “antisense compound” means an antisense oligonucleotide and optionally one or more additional features, such as a conjugate group. As used herein, “sense compound” means a sense oligonucleotide and optionally one or more additional features, such as a conjugate group. As used herein, “antisense oligonucleotide” means an oligonucleotide, including the oligonucleotide portion of an antisense compound, that is capable of hybridizing to a target nucleic acid and is capable of at least one antisense activity. Antisense oligonucleotides include but are not limited to antisense RNAi oligonucleotides and antisense RNase H oligonucleotides. As used herein, “sense oligonucleotide” means an oligonucleotide, including the oligonucleotide portion of a sense compound, that is capable of hybridizing to an antisense oligonucleotide. Sense oligonucleotides include, but are not limited to, sense RNAi oligonucleotides. As used herein, “bicyclic nucleoside” or “BNA” means a nucleoside comprising a bicyclic sugar moiety. As used herein, “bicyclic sugar” or “bicyclic sugar moiety” means a modified sugar moiety comprising two rings, wherein the second ring is formed via a bridge connecting two of the atoms in the first ring thereby forming a bicyclic structure. In certain embodiments, the first ring of the bicyclic sugar moiety is a furanosyl sugar moiety. In certain embodiments, the furanosyl sugar moiety is a ribosyl sugar moiety. In certain embodiments, the bicyclic sugar moiety does not comprise a furanosyl sugar moiety. As used herein, “blunt” or “blunt ended” in reference to an oligomeric duplex formed by two oligonucleotides means that there are no terminal unpaired nucleotides (i.e. no overhanging nucleotides). One or both ends of a double-stranded RNAi agent can be blunt. As used herein, “cell-targeting moiety” means a conjugate moiety or portion of a conjugate moiety that is capable of binding to a particular cell type or particular cell types. As used herein, “cerebrospinal fluid” or “CSF” means the fluid filling the space around the brain and spinal cord. “Artificial cerebrospinal fluid” or “aCSF” means a prepared or manufactured fluid, e.g., as a pharmaceutically acceptable diluent, that has certain properties (e.g., osmolarity, pH, and / or electrolytes) similar to cerebrospinal fluid and is biocompatible with CSF. An aCSF may comprise divalent cation(s) in concentrations described herein. As used herein, “chirally enriched” in reference to a population means a plurality of molecules of identical molecular formula, wherein the number or percentage of molecules within the population that contain a particular stereochemical configuration at a particular chiral center is greater than the number or percentage of molecules expected to contain the same particular stereochemical configuration at the same particular chiral center within the population if the particular chiral center were stereorandom as defined herein. Chirally enriched populations of molecules having multiple chiral centers within each molecule may contain one or more stereorandom chiral centers. In certain embodiments, the molecules are modified oligonucleotides. In certain embodiments, the molecules are oligomeric compounds comprising modified oligonucleotides. In certain embodiments, the chiral center is at the phosphorous atom of a phosphorothioate internucleoside linkage. In certain embodiments, the chiral center is at the phosphorous atom of a mesyl phosphoramidate internucleoside linkage. As used herein, “cleavable moiety” means a bond or group of atoms that is cleaved upon administration to a subject, for example, inside a cell, a subject, or a human. As used herein, “complementary” in reference to an oligonucleotide means that at least 70% of the nucleobases of the oligonucleotide or one or more portions thereof and the nucleobases of another nucleic acid or one or more portions thereof are capable of hydrogen bonding with one another when the nucleobase sequence of the oligonucleotide and the other nucleic acid are aligned in opposing directions. As used herein, “complementary nucleobases” means nucleobases that are capable of forming hydrogen bonds with one another. Complementary nucleobase pairs include adenine (A) and thymine (T), adenine (A) and uracil (U), cytosine (C) and guanine (G), 5-methylcytosine (mC) and guanine (G). Certain modified nucleobases that pair with unmodified nucleobases or with other modified nucleobases are known in the art. For example, inosine can pair with adenosine, cytosine, or uracil. Complementary oligonucleotides and / or nucleic acids need not have nucleobase complementarity at each nucleoside. Rather, some mismatches are tolerated. As used herein, “fully complementary” or “100% complementary” in reference to an oligonucleotide, or a portion thereof, means that the oligonucleotide, or portion thereof, is complementary to another oligonucleotide or nucleic acid at each nucleobase of the shorter of the two oligonucleotides, or at each nucleoside if the oligonucleotides are the same length. As used herein, “complementary region” in reference to an oligonucleotide is the range of nucleobases of the oligonucleotide that is complementary with a second oligonucleotide or target nucleic acid. As used herein, “conjugate group” means a group of atoms directly attached to an oligonucleotide that confers at least one property to the resulting conjugated oligonucleotide. Conjugate groups comprise a conjugate moiety and a conjugate linker that attaches the conjugate moiety to the oligonucleotide. As used herein, “conjugate linker” means a single bond or a group of atoms comprising at least one bond that connects a conjugate moiety to an oligonucleotide. As used herein, “conjugate moiety” means a group of atoms that when covalently bound to a molecule modifies one or more properties of such molecule compared to the identical molecule lacking the conjugate moiety, wherein such properties include, but are not limited to pharmacodynamics, pharmacokinetics, stability, binding, absorption, tissue distribution, cellular distribution, cellular uptake, charge, and clearance. As used herein, “contiguous” in the context of an oligonucleotide refers to nucleosides, nucleobases, sugar moieties, or internucleoside linkages that are immediately adjacent to each other. For example, “contiguous nucleobases” means nucleobases that are immediately adjacent to each other in a sequence. As used herein, “constrained ethyl” or “cEt” or “cEt sugar moiety” means a β-D ribosyl bicyclic sugar moiety wherein the second ring of the bicyclic sugar is formed via a bridge connecting the 4’-carbon and the 2’-carbon of the β-D ribosyl sugar moiety, wherein the bridge has the formula 4'-CH(CH3)-O-2', and wherein the methyl group of the bridge is in the S configuration. As used herein, “cEt nucleoside” means a nucleoside comprising a cEt sugar moiety. As used herein, “deoxy region” means a region of 5-12 contiguous nucleotides, wherein at least 70% of the nucleosides comprise a 2’-deoxy sugar moiety. In certain embodiments, a deoxy region is the gap or internal region of a gapmer. As used herein, “diluent” means an ingredient in a composition that lacks pharmacological activity, but is pharmaceutically necessary or desirable. For example, the diluent in an injected composition can be a liquid, e.g., aCSF, PBS, or saline solution. As used herein, “double-stranded” in reference to a region or an oligonucleotide means a duplex formed by complementary strands of nucleic acids (including, but not limited to oligonucleotides) hybridized to one another. In certain embodiments, the two strands of a double-stranded region are separate molecules. In certain embodiments, the two strands are regions of the same molecule that has folded onto itself (e.g., a hairpin structure). As used herein, “duplex” or “duplex region” means the structure formed by two oligonucleotides or portions thereof that are hybridized to one another. As used herein, “excess” with respect to divalent cation concentration in a pharmaceutical composition means an amount greater than that found in cerebrospinal fluid. In certain embodiments, “excess” divalent cation means more than 1.4 mM Ca+2and / or more than 0.8 mM Mg+2in a composition. In certain embodiments, “excess” divalent cation means Ca+2and Mg+2taken together in a composition are in a concentration more than 2.2 mM. As used herein, “gapmer” means a modified oligonucleotide comprising an internal region having a plurality of nucleosides that support RNase H cleavage positioned between external regions having one or more nucleosides, wherein the nucleosides comprising the internal region are chemically distinct from the nucleoside or nucleosides comprising the external regions. The internal region may be referred to as the “gap” and the external regions may be referred to as the “wings” or “wing segments.” In certain embodiments, the internal region is a deoxy region. The positions of the internal region or gap refer to the order of the nucleosides of the internal region and are counted starting from the 5’-end of the internal region. Unless otherwise indicated, “gapmer” refers to a sugar motif. In certain embodiments, each nucleoside of the gap is a 2’-β-D-deoxynucleoside. In certain embodiments, the gap comprises one 2’-substituted nucleoside at position 1, 2, 3, 4, or 5 of the gap, and the remainder of the nucleosides of the gap are 2’-β-D- deoxynucleosides. As used herein, the term “MOE gapmer” indicates a gapmer having a gap comprising 2’- β-D-deoxynucleosides and wings comprising 2’-MOE nucleosides. As used herein, the term “mixed wing gapmer” indicates a gapmer having wings comprising modified nucleosides comprising at least two different sugar modifications. Unless otherwise indicated, a gapmer may comprise one or more modified internucleoside linkages and / or modified nucleobases and such modifications do not necessarily follow the gapmer pattern of the sugar modifications. As used herein, “hybridization” means the annealing of oligonucleotides and / or nucleic acids. While not limited to a particular mechanism, the most common mechanism of hybridization involves hydrogen bonding, which may be Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleobases. In certain embodiments, complementary nucleic acid molecules include, but are not limited to, an antisense compound and a nucleic acid target. In certain embodiments, complementary nucleic acid molecules include, but are not limited to, an oligonucleotide and a nucleic acid target. As used herein, “internucleoside linkage” means the covalent linkage between contiguous nucleosides in an oligonucleotide. As used herein, “modified internucleoside linkage” means any internucleoside linkage other than a phosphodiester internucleoside linkage. “Phosphorothioate internucleoside linkage” or “PS internucleoside linkage” is a modified internucleoside linkage in which one of the non-bridging oxygen atoms of a phosphodiester internucleoside linkage is replaced with a sulfur atom. As used herein, “inverted nucleoside” means a nucleotide having a 3’ to 3’ and / or 5’ to 5’ internucleoside linkage, as shown herein. As used herein, “inverted sugar moiety” means the sugar moiety of an inverted nucleoside or an abasic sugar moiety having a 3’ to 3’ and / or 5’ to 5’ internucleoside linkage. As used herein, “linked nucleosides” are nucleosides that are connected in a contiguous sequence (i.e., no additional nucleosides are presented between those that are linked). As used herein, “linker-nucleoside” means a nucleoside that links, either directly or indirectly, an oligonucleotide to a conjugate moiety. Linker-nucleosides are located within the conjugate linker of an oligomeric compound. Linker-nucleosides are not considered part of the oligonucleotide portion of an oligomeric compound even if they are contiguous with the oligonucleotide. As used herein, “mismatch” or “non-complementary” means a nucleobase of a first nucleic acid sequence that is not complementary with the corresponding nucleobase of a second nucleic acid sequence or target nucleic acid when the first and second nucleic acid sequences are aligned in opposing directions. As used herein, “motif” means the pattern of unmodified and / or modified sugar moieties, nucleobases, and / or internucleoside linkages, in an oligonucleotide. As used herein, “non-bicyclic modified sugar moiety” means a modified sugar moiety that comprises a modification, such as a substituent, that does not form a bridge between two atoms of the sugar to form a second ring. As used herein, “nucleobase” means an unmodified nucleobase or a modified nucleobase. As used herein an “unmodified nucleobase” is adenine (A), thymine (T), cytosine (C), uracil (U), or guanine (G). As used herein, a “modified nucleobase” is a group of atoms other than unmodified A, T, C, U, or G capable of pairing with at least one unmodified nucleobase. A “5-methylcytosine” is a modified nucleobase. A universal base is a modified nucleobase that can pair with any one of the five unmodified nucleobases. As used herein, “nucleobase sequence” means the order of contiguous nucleobases in a nucleic acid or oligonucleotide independent of any sugar or internucleoside linkage modification. As used herein, “the nucleobase sequence of” a reference SEQ ID NO, refers only to the nucleobase sequence provided in such SEQ ID NO and therefore, unless otherwise indicated, includes compounds wherein each sugar moiety and each internucleoside linkage, independently, may be modified or unmodified, irrespective of the presence or absence of modifications, indicated in the referenced SEQ ID NO. As used herein, “nucleoside” means a compound, or fragment of a compound, comprising a nucleobase and a sugar moiety. The nucleobase and sugar moiety are each, independently, unmodified or modified. As used herein, “modified nucleoside” means a nucleoside comprising a modified nucleobase and / or a modified sugar moiety. “Linked nucleosides” are nucleosides that are connected in a contiguous sequence (i.e., no additional nucleosides are presented between those that are linked). As used herein, "oligomeric agent" means an oligomeric compound and optionally one or more additional features, such as a second oligomeric compound. An oligomeric agent may be a single-stranded oligomeric compound or may be an oligomeric duplex formed by two complementary oligomeric compounds. As used herein, “oligomeric compound” means an oligonucleotide and optionally one or more additional features, such as a conjugate group or terminal group. An oligomeric compound may be paired with a second oligomeric compound that is complementary to the first oligomeric compound or may be unpaired. A “single-stranded oligomeric compound” is an unpaired oligomeric compound. The term “oligomeric duplex” means a duplex formed by two oligomeric compounds having complementary nucleobase sequences. Each oligomeric compound of an oligomeric duplex may be referred to as a “duplexed oligomeric compound.” As used herein, “oligonucleotide” means a polymer of linked nucleosides connected via internucleoside linkages, wherein each nucleoside and internucleoside linkage may be modified or unmodified. Unless otherwise indicated, oligonucleotides consist of 8-50 linked nucleosides. As used herein, “modified oligonucleotide” means an oligonucleotide, wherein at least one nucleoside or internucleoside linkage is modified. As used herein, “unmodified oligonucleotide” means an oligonucleotide that does not comprise any nucleoside modifications or internucleoside modifications. An oligonucleotide may be paired with a second oligonucleotide that is complementary to the oligonucleotide or it may be unpaired. A “single-stranded oligonucleotide” is an unpaired oligonucleotide. A “double-stranded oligonucleotide” is an oligonucleotide that is paired with a second oligonucleotide. As used herein, “pharmaceutically acceptable carrier or diluent” means any substance suitable for use in administering to a subject. Certain such carriers enable pharmaceutical compositions to be formulated as, for example, tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspension and lozenges for the oral ingestion by a subject. In certain embodiments, a pharmaceutically acceptable carrier or diluent is sterile water, sterile saline, sterile buffer solution or sterile artificial cerebrospinal fluid. As used herein, “pharmaceutically acceptable salts” means physiologically and pharmaceutically acceptable salts of compounds. Pharmaceutically acceptable salts retain the desired biological activity of the parent compound and do not impart undesired toxicological effects thereto. As used herein “pharmaceutical composition” means a mixture of substances suitable for administering to a subject. For example, a pharmaceutical composition may comprise an oligomeric compound and a sterile aqueous solution. In certain embodiments, a pharmaceutical composition shows activity in free uptake assay in certain cell lines. As used herein, “reducing or inhibiting the amount or activity” refers to a reduction or blockade of the transcriptional expression or activity relative to the transcriptional expression or activity in an untreated or control sample and does not necessarily indicate a total elimination of transcriptional expression or activity. As used herein, “RNA” means an RNA transcript and includes pre-mRNA and mature mRNA unless otherwise specified. As used herein, “RNAi agent” means an antisense agent that acts, at least in part, through RISC or Ago2 to modulate a target nucleic acid and / or a protein encoded by a target nucleic acid. RNAi agents include, but are not limited to double-stranded siRNA, single-stranded RNAi (ssRNAi), and microRNA, including microRNA mimics. RNAi agents may comprise conjugate groups and / or terminal groups. In certain embodiments, an RNAi agent modulates the amount and / or activity of a target nucleic acid. The term RNAi agent excludes antisense agents that act through RNase H. As used herein, “RNase H agent” means an antisense agent that acts through RNase H to modulate a target nucleic acid and / or protein encoded by a target nucleic acid. In certain embodiments, RNase H agents are single-stranded. In certain embodiments, RNase H agents are double-stranded. RNase H agents may comprise conjugate groups and / or terminal groups. In certain embodiments, an RNase H agent modulates the amount and / or activity of a target nucleic acid. The term RNase H agent excludes antisense agents that act principally through RISC / Ago2. As used herein, “antisense RNase H oligonucleotide” means an oligonucleotide comprising a region that is complementary to a target sequence, and which includes at least one chemical modification suitable for RNase H-mediated nucleic acid reduction. As used herein, “antisense RNAi oligonucleotide” means an oligonucleotide comprising a region that is complementary to a target sequence, and which includes at least one chemical modification suitable for RNAi-mediated nucleic acid reduction. As used herein, “self-complementary” in reference to an oligonucleotide means an oligonucleotide that at least partially hybridizes to itself. As used herein, “single-stranded” means a nucleic acid (including but not limited to an oligonucleotide) that is unpaired and is not part of a duplex. Single-stranded compounds are capable of hybridizing with complementary nucleic acids to form duplexes, at which point they are no longer single- stranded. As used herein, “splice-modulating” means a nucleic acid (including but not limited to an oligonucleotide) that acts, at least in part, by modulating the splicing of a target nucleic acid. In certain embodiments, a splice-modulating oligonucleotide is complementary to a target region that includes a start codon or a stop codon. As used herein, “steric-blocking” means a nucleic acid (including but not limited to an oligonucleotide) that acts, at least in part, due to directly binding to a target nucleic acid, thus blocking the interaction of the target nucleic acid with other nucleic acids or proteins. As used herein, “stabilized phosphate group” means a 5’-phosphate analog that is metabolically more stable than a 5’-phosphate as naturally occurs on DNA or RNA. As used herein, “stereorandom” or “stereorandom chiral center” in the context of a population of molecules of identical molecular formula means a chiral center that is not controlled during synthesis, or enriched following synthesis, for a particular absolute stereochemical configuration. The stereochemical configuration of a chiral center is random when it is the result of a synthetic method that is not designed to control the stereochemical configuration. For example, in a population of molecules comprising a stereorandom chiral center, the number of molecules having the (S) configuration of the stereorandom chiral center may be the same as the number of molecules having the (R) configuration of the stereorandom chiral center (“racemic”). The stereochemical configuration of a chiral center is random when it is the result of a synthetic method that is not designed to control the stereochemical configuration. In certain embodiments, the stereorandom chiral center is at the phosphorous atom of a stereorandom phosphorothioate or mesyl phosphoramidate internucleoside linkage. As used herein, “subject” means a human or non-human animal. In certain embodiments, the subject is a primate. In certain embodiments, the subject is a human. In certain embodiments, a “juvenile subject” in reference to a human means a human under 18 years of age. As used herein, “sugar moiety” means an unmodified sugar moiety or a modified sugar moiety. As used herein, “unmodified sugar moiety” means a 2’-OH(H) β-D-ribosyl sugar moiety, as found in RNA (an “unmodified RNA sugar moiety”), or a 2’-H(H) β-D-deoxyribosyl sugar moiety, as found in DNA (an “unmodified DNA sugar moiety”). Unmodified sugar moieties have one hydrogen at each of the 1’, 3’, and 4’ positions, an oxygen at the 3’ position, and two hydrogens at the 5’ position. As used herein, “modified sugar moiety” or “modified sugar” means a modified furanosyl sugar moiety or a sugar surrogate. As used herein, “sugar surrogate” means a modified sugar moiety having other than a furanosyl moiety that can link a nucleobase to another group, such as an internucleoside linkage, conjugate group, or terminal group in an oligonucleotide. Modified nucleosides comprising sugar surrogates can be incorporated into one or more positions within an oligonucleotide and such oligonucleotides are capable of hybridizing to complementary oligomeric compounds or target nucleic acids. As used herein, “symptom” means any physical feature or test result that indicates the existence or extent of a disease or disorder. In certain embodiments, a symptom is apparent to a subject or to a medical professional examining or testing said subject. In certain embodiments, symptoms include muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, seizures, nystagmus, increased muscle cramping or spasms, convulsions, urinary incontinence, lethargy, loss of lower spinal reflexes, inhibition of upper and / or lower extremities, paresis, hypoactivity, or death. As used herein, “target nucleic acid” and “target RNA” mean a nucleic acid that an antisense compound is designed to affect. Target RNA means an RNA transcript and includes pre-mRNA and mature mRNA unless otherwise specified. As used herein, “target region” means a portion of a target nucleic acid to which an oligomeric compound is designed to hybridize. As used herein, “terminal group” means a chemical group or group of atoms that is covalently linked to a terminus of an oligonucleotide. As used herein, “treating” means improving a subject’s disease or condition by administering an oligomeric compound described herein. In certain embodiments, treating a subject improves a symptom relative to the same symptom in the absence of the treatment. In certain embodiments, treatment reduces in the severity or frequency of a symptom, or delays the onset of a symptom, slows the progression of a symptom, or slows the severity or frequency of a symptom. As used herein, “therapeutically effective amount” means an amount of a pharmaceutical agent or composition that provides a therapeutic benefit to a subject. For example, a therapeutically effective amount improves a symptom of a disease. As used herein, the term “neurotoxicity” refers to the nonhybridization dependent neurobehavioral side effects observed in a subject upon administration of an oligomeric compound. Neurotoxicity that occurs shortly after dosing (e.g., within a few hours) is referred to herein as “acute neurotoxicity”. Acute neurotoxicity can be further subdivided into an activation and an inhibition neurobehavioral phenotype, termed herein as “acute activation” and “acute sedation”. The acute neurobehavioral phenotypes can include activation of a muscle group or inactivation of a muscle group in a subject. Exemplary phenotypes include, but are not limited to, muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, seizures, nystagmus, increased muscle cramping or spasms, convulsions, urinary incontinence, lethargy, loss of lower spinal reflexes, inhibition of upper and / or lower extremities, paresis, hypoactivity, or death. The term “acute activation” or “aA” refers to nonhybridization dependent neurobehavioral side effects that involve movement or activation of a muscle group in the subject. Neurobehavioral phenotypes for acute activation are generally transient, and can include muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, nystagmus, urinary incontinence, increased muscle cramping or spasms, convulsions, or seizures. Neurobehavioral phenotypes can also include vocalization in the subject, e.g., in a primate. The term “acute sedation” refers to nonhybridization dependent neurobehavioral side effects that involve an inactivation or inhibition of a muscle group in the subject. Neurobehavioral phenotypes for acute sedation are generally transient, and can include lethargy, loss of lower spinal reflexes, inhibition of upper and / or lower extremities, paresis, or hypoactivity. As used herein, the term “ratio” in the context of divalent cation to an oligomeric compound is a molar ratio. The molar ratio is defined by the total molar concentration of a divalent cation in a pharmaceutical composition divide by the total molar concentration of the oligomeric compound in the pharmaceutical composition. CERTAIN EMBODIMENTS The present disclosure provides the following non-limiting numbered embodiments: Embodiment 1. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1. Embodiment 2. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1. Embodiment 3. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the total concentration of the divalent cation is greater than 2.2 mM. Embodiment 4. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. Embodiment 5. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the total concentration of the divalent cation is greater than 2.2 mM, and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. Embodiment 6. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and artificial cerebrospinal fluid (aCSF) comprising an excess of a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1. Embodiment 7. The pharmaceutical composition of embodiment 3, wherein the molar ratio of the divalent cation to the oligomeric compound is from 2 to 7.1. Embodiment 8. The pharmaceutical composition of any of embodiments 1-3, 6, or 7, wherein the molar ratio of the divalent cation to the oligomeric compound is from 2 to 6, 2 to 5.2, 2 to 5, 3 to 6, 3 to 5.2, 3 to 5, 2.3-5.2, or 2 to 4. Embodiment 9. The pharmaceutical composition of any of embodiments 1-3 or 6-8, wherein the molar ratio of the divalent cation to the oligomeric compound is from 2 to 3. Embodiment 10. The pharmaceutical composition of any of embodiments 2, 3, 5, or 6, wherein the concentration of the oligomeric compound is 1.2 mM or higher. Embodiment 11. The pharmaceutical composition of any of embodiments 1-10, wherein the concentration of the oligomeric compound is 2 mM or higher, 3 mM or higher, 4 mM or higher, or 5 mM or higher. Embodiment 12. The pharmaceutical composition of any of embodiments 1-10, wherein the concentration of the oligomeric compound is from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM. Embodiment 13. The pharmaceutical composition of any of embodiments 1, 2, 4, or 6, wherein the total concentration of the divalent cation is greater than 2.2 mM. Embodiment 14. The pharmaceutical composition of any of embodiments 1-13, wherein the total concentration of the divalent cation is 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, or 15 mM or higher. Embodiment 15. The pharmaceutical composition of any of embodiments 1-13, wherein the total concentration of the divalent cation is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, or from 15 mM to 30 mM. Embodiment 16. The pharmaceutical composition of any of embodiments 1-15, wherein the divalent cation is selected from Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, Zn2+, or a combination thereof. Embodiment 17. The pharmaceutical composition of embodiment 16, wherein the divalent cation is selected from Ca2+, Mg2+, Zn2+, or a combination thereof. Embodiment 18. The pharmaceutical composition of embodiment 16, wherein the divalent cation is selected from Ca2+, Mg2+, or a combination thereof. Embodiment 19. The pharmaceutical composition of embodiment 16, wherein the divalent cation is Ca2+. Embodiment 20. The pharmaceutical composition of embodiment 16, wherein the divalent cation is Mg2+. Embodiment 21. The pharmaceutical composition of any of embodiments 1-20, wherein the pharmaceutically acceptable diluent comprises artificial cerebrospinal fluid (aCSF). Embodiment 22. The pharmaceutical composition of any of embodiments 1-20, wherein the pharmaceutically acceptable diluent comprises phosphate-buffered saline (PBS). Embodiment 23. The pharmaceutical composition of any of embodiments 1-22, wherein the oligomeric compound comprises a modified oligonucleotide consisting of 12 to 30 linked nucleosides. Embodiment 24. The pharmaceutical composition of embodiment 23, wherein the modified oligonucleotide consists of 12 to 20, 12 to 25, 12 to 30, 13 to 20, 13 to 25, 13 to 30, 14 to 20, 14 to 25, 14 to 30, 15 to 20, 15 to 25, 15 to 30, 16 to 18,16 to 20, 16 to 25, 16 to 30, 17 to 20, 17 to 25, 17 to 30, 18 to 20, 18 to 25, 18 to 30, 19 to 20, 19 to 25, 19 to 30, 20 to 25, or 20 to 30 linked nucleosides. Embodiment 25. The pharmaceutical composition of embodiment 23 or 24, wherein the modified oligonucleotide consists of 16, 17, 18, 19, or 20 linked nucleosides. Embodiment 26. The pharmaceutical composition of any of embodiments 23-25, wherein the modified oligonucleotide consists of 20 linked nucleosides. Embodiment 27. The pharmaceutical composition of any of embodiments 1-26, wherein the modified oligonucleotide has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or 20 contiguous nucleobases of SEQ ID NOs: 92-94. Embodiment 28. The pharmaceutical composition of any of embodiments 1-26, wherein the modified oligonucleotide consists of SEQ ID NOs: 92-94. Embodiment 29. The pharmaceutical composition of any of embodiments 1-28, wherein the modified oligonucleotide comprises a modified nucleoside. Embodiment 30. The pharmaceutical composition of embodiment 29, wherein the modified nucleoside comprises a modified sugar moiety. Embodiment 31. The pharmaceutical composition of embodiment 30, wherein the modified sugar moiety comprises a bicyclic sugar moiety. Embodiment 32. The pharmaceutical composition of embodiment 31, wherein the bicyclic sugar moiety comprises a 2’-4’ bridge selected from -O-CH2-; and -O-CH(CH3)-. Embodiment 33. The pharmaceutical composition of embodiment 30, wherein the modified sugar moiety comprises a non-bicyclic modified sugar moiety. Embodiment 34. The pharmaceutical composition of embodiment 33, wherein the non-bicyclic modified sugar moiety is a 2’-MOE sugar moiety, a 2’-OMe sugar moiety, 2’-NMA, or a 2’-β-D- deoxyxylosyl sugar moiety. Embodiment 35. The pharmaceutical composition of embodiment 30, wherein the modified sugar moiety comprises a sugar surrogate. Embodiment 36. The pharmaceutical composition of embodiment 35, wherein the sugar surrogate is any of morpholino, modified morpholino, glycol nucleic acid (GNA), six-membered tetrahydropyran (THP), and F-hexitol nucleic acid (F-HNA). Embodiment 37. The pharmaceutical composition of any of embodiments 1-36, wherein the modified oligonucleotide comprises at least one modified internucleoside linkage. Embodiment 38. The pharmaceutical composition of embodiment 37, wherein at least one internucleoside linkage is a phosphodiester internucleoside linkage. Embodiment 39. The pharmaceutical composition of embodiment 37 or embodiment 38, wherein at least one modified internucleoside linkage is a phosphorothioate internucleoside linkage. Embodiment 40. The pharmaceutical composition of any of embodiments 37-39, wherein at least one modified internucleoside linkage is a mesyl phosphoramidate internucleoside linkage. Embodiment 41. The pharmaceutical composition of any of embodiments 37-40, wherein each internucleoside linkage is independently selected from a phosphodiester internucleoside linkage, a phosphorothioate internucleoside linkage, and a mesyl phosphoramidate internucleoside linkage. Embodiment 42. The pharmaceutical composition of any of embodiments 37, 39, or 40, wherein each internucleoside linkage is independently selected from a phosphorothioate internucleoside linkage and a mesyl phosphoramidate internucleoside linkage. Embodiment 43. The pharmaceutical composition of any of embodiments 37-39, wherein each internucleoside linkage is independently selected from a phosphodiester internucleoside linkage and a phosphorothioate internucleoside linkage. Embodiment 44. The pharmaceutical composition of any of embodiments 37, 39, or 41-43, wherein each internucleoside linkage is a phosphorothioate internucleoside linkage. Embodiment 45. The pharmaceutical composition of any of embodiments 1-44, wherein at least one nucleoside of the modified oligonucleotide comprises a modified nucleobase. Embodiment 46. The pharmaceutical composition of embodiment 45, wherein the modified nucleobase is a 5-methylcytosine. Embodiment 47. The pharmaceutical composition of embodiment 46, wherein each cytosine is a 5- methylcytosine. Embodiment 48. The pharmaceutical composition of any of embodiments 1-46, wherein each nucleoside of the modified oligonucleotide is unmodified adenine, unmodified guanine, unmodified thymine, unmodified cytosine, modified adenine, or 5-methylcytosine. Embodiment 49. The pharmaceutical composition of any of embodiments 1-48, wherein the modified oligonucleotide comprises a deoxy region. Embodiment 50. The pharmaceutical composition of embodiment 49, wherein each nucleoside of the deoxy region is a 2’-β-D-deoxynucleoside. Embodiment 51. The pharmaceutical composition of embodiment 49 or embodiment 50, wherein the deoxy region consists of 6, 7, 8, 9, 10, or 6-10 linked nucleosides. Embodiment 52. The pharmaceutical composition of any of embodiments 49-51, wherein each nucleoside immediately adjacent to the deoxy region comprises a modified sugar moiety. Embodiment 53. The pharmaceutical composition of any of embodiments 49-51, wherein the deoxy region is flanked on the 5’-side by a 5’-region consisting of 1-6 linked 5’-region nucleosides and on the 3’- side by a 3’-region consisting of 1-6 linked 3’-region nucleosides; wherein at least one nucleoside of the 5’- region comprises a modified sugar moiety; and at least one nucleoside of the 3’-region comprises a modified sugar moiety. Embodiment 54. The pharmaceutical composition of embodiment 53, wherein each nucleoside of the 5’-region comprises a modified sugar moiety. Embodiment 55. The pharmaceutical composition of embodiment 53 or embodiment 54, wherein each nucleoside of the 3’-region comprises a modified sugar moiety. Embodiment 56. The pharmaceutical composition of any of embodiments 1-55, wherein the oligomeric compound consists of the modified oligonucleotide. Embodiment 57. The pharmaceutical composition of any of embodiments 1-55, wherein the oligomeric compound comprises a conjugate group. Embodiment 58. The pharmaceutical composition of embodiment 57, wherein the conjugate group comprises a conjugate moiety and a conjugate linker. Embodiment 59. The pharmaceutical composition of embodiment 58, wherein the conjugate linker is a phosphodiester linker. Embodiment 60. The pharmaceutical composition of embodiment 58, wherein the conjugate linker consists of a single bond. Embodiment 61. The pharmaceutical composition of any of embodiments 58-60, wherein the conjugate linker is cleavable. Embodiment 62. The pharmaceutical composition of any of embodiments 58, 59, or 61, wherein the conjugate linker comprises 1-3 linker-nucleosides, wherein at least one linker nucleoside is linked to the conjugate moiety, to the modified oligonucleotide, or to another linker-nucleoside by a phosphodiester bond. Embodiment 63. The pharmaceutical composition of any of embodiments 58-62, wherein the conjugate group is attached to the modified oligonucleotide at the 5’ end of the modified oligonucleotide. Embodiment 64. The pharmaceutical composition of any of embodiments 58-62, wherein the conjugate group is attached to the modified oligonucleotide at the 3’ end of the modified oligonucleotide. Embodiment 65. The pharmaceutical composition of any of embodiments 1-61 or 63-64, wherein the oligomeric compound does not comprise linker-nucleosides. Embodiment 66. The pharmaceutical composition of any of embodiments 1-65, comprising a terminal group. Embodiment 67. The pharmaceutical composition of embodiment 66, wherein the terminal group is an abasic sugar moiety. Embodiment 68. The pharmaceutical composition of any of embodiments 1-67, wherein the oligomeric compound is a single-stranded oligomeric compound. Embodiment 69. The pharmaceutical composition of any of embodiments 1-68, wherein the oligomeric compound is a single-stranded RNase H agent. Embodiment 70. The pharmaceutical composition of any of embodiments 1-68, wherein the oligomeric compound is an antisense compound. Embodiment 71. The pharmaceutical composition of any of embodiments 1-67, wherein the oligomeric compound is a splice-modulating oligomeric compound. Embodiment 72. The pharmaceutical composition of any of embodiments 1-67, wherein the oligomeric compound is steric-blocking oligomeric compound. Embodiment 73. The pharmaceutical composition of any of embodiments 1-67, or 70-72, wherein the pharmaceutical composition further comprises a second oligomeric compound comprising a second modified oligonucleotide, wherein the second oligomeric compound hybridizes to the oligomeric compound to form an oligomeric duplex. Embodiment 74. The pharmaceutical composition of embodiment 73, wherein the second modified oligonucleotide consists of 12 to 30 linked nucleosides, and wherein the nucleobase sequence of the second modified oligonucleotide comprises a complementary region of at least 8 nucleobases that is at least 90% complementary to an equal length portion of the modified oligonucleotide. Embodiment 75. The pharmaceutical composition of embodiment 73 or embodiment 74, wherein at least one nucleoside of the second modified oligonucleotide comprises a modified sugar moiety. Embodiment 76. The pharmaceutical composition of embodiment 75, wherein the modified sugar moiety of the second modified oligonucleotide comprises a bicyclic sugar moiety. Embodiment 77. The pharmaceutical composition of embodiment 76, wherein the bicyclic sugar moiety of the second modified oligonucleotide comprises a 2’-4’ bridge selected from –O-CH2-; and –O- CH(CH3)-. Embodiment 78. The pharmaceutical composition of embodiment 75, wherein the modified sugar moiety of the second modified oligonucleotide comprises a non-bicyclic modified sugar moiety. Embodiment 79. The pharmaceutical composition of embodiment 78, wherein the non-bicyclic modified sugar moiety of the second modified oligonucleotide is a 2’-MOE sugar moiety, a 2’-F modified sugar moiety, or 2’-OMe modified sugar moiety. Embodiment 80. The pharmaceutical composition of any of embodiments 73-79, wherein at least one internucleoside linkage of the second modified oligonucleotide is a modified internucleoside linkage. Embodiment 81. The pharmaceutical composition of embodiment 80, wherein at least one modified internucleoside linkage of the second modified oligonucleotide is a phosphorothioate internucleoside linkage. Embodiment 82. The pharmaceutical composition of any of embodiments 73-81, wherein at least one internucleoside linkage of the second modified oligonucleotide is a phosphodiester internucleoside linkage. Embodiment 83. The pharmaceutical composition of any of embodiments 80-82, wherein at least one internucleoside linkage of the second modified oligonucleotide is a mesyl phosphoramidate internucleoside linkage. Embodiment 84. The pharmaceutical composition of any of embodiments 73-83, wherein each internucleoside linkage of the second modified oligonucleotide is independently selected from a phosphodiester internucleoside linkage, a phosphorothioate internucleoside linkage, or a mesyl phosphoramidate internucleoside linkage. Embodiment 85. The pharmaceutical composition of any of embodiments 73-84, wherein the second modified oligonucleotide comprises at least one modified nucleobase. Embodiment 86. The pharmaceutical composition of embodiment 85, wherein the at least one modified nucleobase of the second modified oligonucleotide is 5-methylcytosine. Embodiment 87. The pharmaceutical composition of any of embodiments 73-86, wherein the second modified oligonucleotide comprises a conjugate group. Embodiment 88. The pharmaceutical composition of embodiment 87, wherein the conjugate group comprises a conjugate moiety and a conjugate linker. Embodiment 89. The pharmaceutical composition of embodiment 88, wherein the conjugate linker consists of a single bond. Embodiment 90. The pharmaceutical composition of embodiment 88 or embodiment 89, wherein the conjugate linker is cleavable. Embodiment 91. The pharmaceutical composition of any of embodiments 88 or 90, wherein the conjugate linker comprises 1-3 linker-nucleosides, wherein at least one linker nucleoside is linked to the conjugate moiety, to the second modified oligonucleotide, or to another linker-nucleoside by a phosphodiester bond. Embodiment 92. The pharmaceutical composition of any of embodiments 88-91, wherein the conjugate linker is a phosphodiester linker. Embodiment 93. The pharmaceutical composition of any of embodiments 87-92, wherein the conjugate group is attached to the 5’-end of the second modified oligonucleotide. Embodiment 94. The pharmaceutical composition of any of embodiments 87-92, wherein the conjugate group is attached to the 3’-end of the second modified oligonucleotide. Embodiment 95. The pharmaceutical composition of any of embodiments 87-92, wherein the conjugate group is attached via the 2’ position of a ribosyl sugar moiety at an internal position of the second modified oligonucleotide. Embodiment 96. The pharmaceutical composition of any of embodiments 87-95, wherein the conjugate group comprises a C22 alkyl, C20 alkyl, C16 alkyl, C10 alkyl, C21 alkyl, C19 alkyl, C18 alkyl, C17 alkyl, C15 alkyl, C14 alkyl, C13 alkyl, C12 alkyl, C11 alkyl, C9 alkyl, C8 alkyl, C7 alkyl, C6 alkyl, C5 alkyl, C22 alkenyl, C20 alkenyl, C16 alkenyl, C10 alkenyl, C21 alkenyl, C19 alkenyl, C18 alkenyl, C17 alkenyl, C15 alkenyl, C14 alkenyl, C13 alkenyl, C12 alkenyl, C11 alkenyl, C9 alkenyl, C8 alkenyl, C7 alkenyl, C6 alkenyl, or C5 alkenyl. Embodiment 97. The pharmaceutical composition of any of embodiments 87-96, wherein the conjugate group comprises a cell-targeting moiety. Embodiment 98. The pharmaceutical composition of any of embodiments 73-97, wherein the second modified oligonucleotide comprises a terminal group. Embodiment 99. The pharmaceutical composition of embodiment 98, wherein the terminal group is an abasic sugar moiety. Embodiment 100. The pharmaceutical composition of any of embodiments 73-99, wherein the modified oligonucleotide comprises a 5’-stabilized phosphate group. Embodiment 101. The pharmaceutical composition of embodiment 100, wherein the stabilized phosphate group comprises a cyclopropyl phosphonate or a vinyl phosphonate. Embodiment 102. The pharmaceutical composition of any of embodiments 73-101, wherein the total concentration of the divalent cation is lower than 10 mM, lower than 8 mM, lower than 5 mM, or lower than 3 mM. Embodiment 103. The pharmaceutical composition of any of embodiments 73-102, wherein the molar ratio of the divalent cation to the oligomeric duplex is from 2 to 7.1. Embodiment 104. The pharmaceutical composition of any of embodiments 73-103, wherein the molar ratio of the divalent cation to the oligomeric duplex is 2 to 6, 2 to 5.2, 2 to 5, 3 to 6, 3 to 5.2, 3 to 5, 2.3 to 5.2, or 2 to 4. Embodiment 105. The pharmaceutical composition of any of embodiments 73-103, wherein the molar ratio of the divalent cation to the oligomeric duplex is from 2 to 3. Embodiment 106. The pharmaceutical composition of any of embodiments 73-105, wherein the concentration of the oligomeric duplex is 1.2 mM or higher. Embodiment 107. The pharmaceutical composition of any of embodiments 73-106, wherein the concentration of the oligomeric duplex is 2 mM or higher, 3 mM or higher, 4 mM or higher, or 5 mM or higher. Embodiment 108. The pharmaceutical composition of any of embodiments 1-107, wherein the pharmaceutical composition consists essentially of or consists of the oligomeric compound, aCSF, and an excess amount of a divalent cation selected from Ca2+and Mg2+. Embodiment 109. The pharmaceutical composition of any of embodiments 1-108, wherein the pharmaceutical composition consists essentially of or consists of the oligomeric compound, aCSF, and an excess amount of Ca2+divalent cation. Embodiment 110. The pharmaceutical composition of any of embodiments 1-108, wherein the pharmaceutical composition consists essentially of or consists of the oligomeric compound, aCSF, and an excess amount of Mg2+divalent cation. Embodiment 111. The pharmaceutical composition of any of embodiments 1-107, wherein the pharmaceutical composition consists essentially of or consists of the oligomeric compound, PBS, and an excess amount of a divalent cation selected from Ca2+and Mg2+. Embodiment 112. The pharmaceutical composition of any of embodiments 1-107 or 111, wherein the pharmaceutical composition consists essentially of or consists of the oligomeric compound, PBS, and an excess amount of Ca2+divalent cation. Embodiment 113. The pharmaceutical composition of any of embodiments 1-107 or 111, wherein the pharmaceutical composition consists essentially of or consists of the oligomeric compound, PBS, and an excess amount of Mg2+divalent cation. Embodiment 114. Use of a pharmaceutical composition of any of embodiments 1–113 for treating a neurodegenerative disease or a neurodevelopmental disorder in a subject. Embodiment 115. Use of a pharmaceutical composition of any of embodiments 1–113 in the manufacture of a medicament for treating a neurodegenerative disease or a neurodevelopmental disorder in a subject. Embodiment 116. A method comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition of any of embodiments 1-113. Embodiment 117. A method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1, and wherein the subject is a primate. Embodiment 118. A method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1, and wherein the subject is a primate. Embodiment 119. A method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the total concentration of the divalent cation is greater than 2.2 mM and wherein the subject is a primate. Embodiment 120. A method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. Embodiment 121. A method administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the total concentration of the divalent cation is greater than 2.2 mM and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. Embodiment 122. A method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and artificial cerebrospinal fluid (aCSF) comprising an excess of a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound to from 2 to 7.1. Embodiment 123. The method or use of any of embodiments 114-122, wherein the nucleobase sequence of the modified oligonucleotide is at least 80%, 85%, 90%, or 95%, or is 100% complementary to an equal length portion of a target nucleic acid. Embodiment 124. The method or use of embodiment 123, wherein the target nucleic acid is expressed in a cell of the central nervous system (CNS). Embodiment 125. The method or use of embodiment 124, wherein the target nucleic acid is expressed in a brain cell. Embodiment 126. The method or use of embodiment 124, wherein the target nucleic acid is expressed in a neuron. Embodiment 127. The method or use of embodiment 124, wherein the target nucleic acid is expressed in a glial cell. Embodiment 128. The method or use of embodiment 127, wherein the target nucleic acid is expressed in an oligodendrocyte, an astrocyte, a microglia, or an ependymal cell, or its respective progenitor cell. Embodiment 129. The method or use of any of embodiments 123-128, wherein the target nucleic acid is APOE, APP, ATXN1, ATXN2, ATXN3, C9ORF72, GFAP, GYS1, HTT, KCNT1, LRRK2, PLP1, PMP22, PRNP, SMN2, SNCA, STMN2, or UBE3A-ATS. Embodiment 130. The method or use of any of embodiments 114-129, wherein the subject has a neurodegenerative disease or a neurodevelopmental disorder. Embodiment 131. The method or use of embodiment 130, wherein the neurodegenerative disease or neurodevelopmental disorder is dementia, a channelopathy, a tauopathy, a synucleinopathy, or a spinocerebellar ataxia. Embodiment 132. The method or use of embodiment 130, wherein the neurodegenerative disease or neurodevelopmental disorder is Alexander disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Angelman Syndrome, Charcot-Marie-Tooth disease, epilepsy, Friedreich ataxia, frontotemporal dementia, Huntington’s disease, Lafora disease, Lewy body disease, Parkinson’s disease, Pelizaeus-Merzbacher disease, prion disease, or spinal muscular atrophy. Embodiment 133. The method or use of any of embodiments 114-132, wherein the pharmaceutical composition ameliorates an acute neurotoxicity in the subject. Embodiment 134. The method or use of any of embodiments 114-132, wherein the pharmaceutical composition prevents an acute neurotoxicity in the subject. Embodiment 135. The method or use of embodiment 133 or 134, wherein the acute neurotoxicity is an acute activation. Embodiment 136. The method or use of embodiment 135, wherein the acute activation lasts no more than 120 minutes, no more than 90 minutes, no more than 60 minutes, no more than 50 minutes, no more than 45 minutes, no more than 40 minutes, no more than 35 minutes, no more than 30 minutes, no more than 25 minutes, no more than 20 minutes, no more than 15 minutes, no more than 10 minutes, or no more than 5 minutes in the subject post administration. Embodiment 137. The method or use of embodiment 135 or 136, wherein a symptom of an acute activation improves or is resolved in 120 minutes, 90 minutes, 60 minutes, 50 minutes, 45 minutes, 40 minutes, 35 minutes, 30 minutes, 25 minutes, 20 minutes, 15 minutes, or 10 minutes post symptom onset. Embodiment 138. The method or use of embodiment 137, wherein the symptom is muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, nystagmus, urinary incontinence, increased muscle cramping or spasms, convulsions, or seizures. Embodiment 139. The method or use of embodiment 135, wherein the pharmaceutical composition prevents an acute activation in the subject. Embodiment 140. The method or use of any of embodiments 114-139, wherein the pharmaceutical composition does not induce an acute sedation. Embodiment 141. The method or use of any of embodiments 114-140, wherein the pharmaceutical composition is administered by intrathecal or intracerebroventricular administration. Embodiment 142. The method or use of any of preceding embodiments, wherein the subject is a human. Embodiment 143. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 0.11*n to 0.37*n, wherein n is the number of anionic phosphate moieties in the modified oligonucleotide. Embodiment 144. The pharmaceutical composition of embodiment 143, wherein the total concentration of the divalent cation is greater than 2.2 mM. Embodiment 145. The pharmaceutical composition of embodiment 143 or 144, wherein the oligomeric compound has a concentration of 1.2 mM or higher. Embodiment 146. The pharmaceutical composition of any of embodiments 143-145, wherein n is from 13 to 43, from 17 to 43, from 18 to 43, or from 19 to 43. CERTAIN PHARMACEUTICAL COMPOSITIONS Provided herein are pharmaceutical compositions comprising an oligomeric compound and a pharmaceutically acceptable diluent wherein the pharmaceutical composition is formulated to ameliorate an acute neurotoxicity in a subject in need thereof. Also provided herein are pharmaceutical compositions comprising an oligomeric compound and a pharmaceutically acceptable diluent wherein the pharmaceutical composition is formulated to prevent an acute neurotoxicity in a subject in need thereof. In certain embodiments, the pharmaceutically acceptable diluent comprising an amount of a divalent cation, wherein the amount of the divalent cation ameliorates or prevents the acute neurotoxicity. In certain embodiments, the amount of a divalent cation in a pharmaceutically acceptable diluent reduces the frequency of an acute neurotoxicity, decreases the duration of an acute neurotoxicity, and / or decreases the intensity of an acute neurotoxicity. In certain embodiments, the acute neurotoxicity is an acute activation. In certain embodiments, administration of a pharmaceutical composition comprising a pharmaceutically acceptable diluent comprising an amount of a divalent cation decreases one or more phenotypes associated with the acute activation. In certain embodiments, administration of a pharmaceutical composition comprising an amount of a divalent cation decreases muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, nystagmus, urinary incontinence, increased muscle cramping or spasms, convulsions, and / or seizures. I. Certain Pharmaceutically Acceptable Diluents Provided herein are pharmaceutical compositions comprising a pharmaceutically acceptable diluent. In certain embodiments, the pharmaceutically acceptable diluent is artificial cerebrospinal fluid (artificial CSF or aCSF), phosphate-buffered saline (PBS), saline, or water, in which the concentration of divalent cation(s) is sufficient to ameliorate or prevent development of an acute neurotoxicity in a subject compared to administration of a typical formulation of an oligomeric compound, e.g., in a typical aCSF. In certain embodiments, the aCSF, PBS, saline, and water are sterile aCSF, sterile PBS, sterile saline, and sterile water. In certain embodiments, the aCSF, PBS, saline, and water are pharmaceutical grade aCSF, pharmaceutical grade PBS, pharmaceutical grade saline, and pharmaceutical grade water. In certain embodiments, the PBS is Dulbecco’s phosphate-buffered saline (DPBS), wherein the PBS is without calcium or magnesium. In certain embodiments, a pharmaceutical composition comprises an oligomeric compound comprising a modified oligonucleotide and artificial cerebrospinal fluid (aCSF), with an excess amount of a divalent cation described below. In certain embodiments, a pharmaceutical composition consists of an oligomeric compound comprising a modified oligonucleotide and artificial cerebrospinal fluid with an excess amount of a divalent cation. In certain embodiments, a pharmaceutical composition consists essentially of an oligomeric compound comprising a modified oligonucleotide and artificial cerebrospinal fluid with an excess amount of a divalent cation. In certain embodiments, the artificial cerebrospinal fluid is pharmaceutical grade. In certain embodiments, aCSF inherently comprises sodium chloride, potassium chloride, sodium dihydrogen phosphate dihydrate, sodium phosphate dibasic anhydrous, calcium chloride dihydrate, and magnesium chloride hexahydrate. The concentrations of respective salts in aCSF can be 150 mM of sodium chloride, 3 mM of potassium chloride, 0.32 mM of sodium dihydrogen phosphate dihydrate, 0.68 mM of sodium phosphate dibasic anhydrous, 1.4 mM of calcium chloride dihydrate, and 0.8 mM of magnesium chloride hexahydrate. The respective aCSF ion concentrations can be 150 mM of Na+, 3 mM of K+, 1.4 mM of Ca2+, 0.8 mM of Mg2+, 1 mM of phosphate ions and 155 mM of Cl-. The total concentration of calcium and magnesium cations inherent in aCSF is 2.2 mM. In certain embodiments, the pH of an aCSF solution is modulated with a suitable pH-adjusting agent, for example, with acids such as hydrochloric acid and alkalis such as sodium hydroxide, to a range of 7.1-7.3, or to 7.2. In certain embodiments, a divalent cation described below is further added to aCSF. In certain embodiments, the aCSF is sodium-deficient artificial cerebrospinal fluid (dACSF) containing 3 mM of potassium chloride, 0.32 mM of sodium dihydrogen phosphate dihydrate, 0.68 mM of sodium phosphate dibasic anhydrous, 1.4 mM of calcium chloride dihydrate, and 0.8 mM of magnesium chloride hexahydrate, and 0-96 mM sodium chloride, e.g., 0 mM, 42 mM, or 96 mM sodium chloride. In certain embodiments, the aCSF is modified artificial cerebrospinal fluid (mACSF) containing 150 mM of sodium chloride, 3 mM of potassium chloride, 0.32 mM of sodium dihydrogen phosphate dihydrate, and 0.68 mM of sodium phosphate dibasic anhydrous. In certain embodiments, a pharmaceutical composition comprises an oligomeric compound comprising a modified oligonucleotide and phosphate-buffered saline (PBS), with an excess concentration of a divalent cation described below. In certain embodiments, a pharmaceutical composition consists of an oligomeric compound comprising a modified oligonucleotide and PBS with an excess concentration of a divalent cation. In certain embodiments, a pharmaceutical composition consists essentially of an oligomeric compound comprising a modified oligonucleotide and PBS with an excess concentration of a divalent cation. In certain embodiments, the PBS is pharmaceutical grade. In certain embodiments, the PBS is DPBS. In certain embodiments, PBS comprises sodium chloride, potassium chloride, sodium phosphate dibasic, and potassium phosphate dibasic. The concentrations of respective salts in PBS can be 137 mM sodium chloride, 2.7 mM potassium chloride, 10 mM sodium phosphate dibasic, and 1.8 mM potassium phosphate dibasic. In certain embodiments, the pH of a PBS solution is modulated with a suitable pH- adjusting agent, for example, with acids such as hydrochloric acid and alkalis such as sodium hydroxide, to a range of 7.1-7.4, or to 7.4 or to 7.2. In certain embodiments, a divalent cation described below is further added to PBS. II. Certain Divalent Cations and Concentrations Thereof Provided herein are pharmaceutical compositions comprising a pharmaceutically acceptable diluent comprising an amount of a divalent cation that ameliorates or prevents an acute neurotoxicity. In certain embodiments, the divalent cation is Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+. In certain embodiments, the divalent cation is Ca2+, Mg2+, Fe2+, or Zn2+. In certain embodiments, the divalent cation is Ca2+or Mg2+. In certain embodiments, the divalent cation is Ba2+. In certain embodiments, the divalent cation is Be2+. In certain embodiments, the divalent cation is Ca2+. In certain embodiments, the divalent cation is Cu2+. In certain embodiments, the divalent cation is Fe2+. In certain embodiments, the divalent cation is Mg2+. In certain embodiments, the divalent cation is Mn2+. In certain embodiments, the divalent cation is Ni2+. In certain embodiments, the divalent cation is Zn2+. In certain embodiments, the total concentration of a divalent cation in the pharmaceutically acceptable diluent is greater than 2.2 mM. In certain embodiments, the total concentration of a divalent cation is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In some embodiments, the pharmaceutically acceptable diluent comprises a single divalent cation. In other embodiments, the pharmaceutically acceptable diluent comprises a combination of divalent cations. In certain embodiments, the pharmaceutically acceptable diluent comprises Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or a combination thereof. In certain embodiments, the pharmaceutically acceptable diluent comprises Ca2+, Mg2+, or Zn2+, or a combination thereof. In certain embodiments, the pharmaceutically acceptable diluent comprises Ca2+or Mg2+, or a combination thereof. In certain embodiments, the pharmaceutically acceptable diluent comprises Ba2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Be2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Ca2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Cu2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Fe2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Mg2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Mn2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Ni2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Zn2+. In certain embodiments, the total concentration of a divalent cation in the pharmaceutically acceptable diluent is from 2.3 mM to 40 mM. In certain embodiments, the total concentration of a divalent cation is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In some embodiments, the pharmaceutically acceptable diluent comprises a single divalent cation. In other embodiments, the pharmaceutically acceptable diluent comprises a combination of divalent cations. In certain embodiments, the pharmaceutically acceptable diluent comprises Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or a combination thereof. In certain embodiments, the pharmaceutically acceptable diluent comprises Ca2+, Mg2+, or Zn2+, or a combination thereof. In certain embodiments, the pharmaceutically acceptable diluent comprises Ca2+or Mg2+, or a combination thereof. In certain embodiments, the pharmaceutically acceptable diluent comprises Ba2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Be2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Ca2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Cu2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Fe2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Mg2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Mn2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Ni2+. In certain embodiments, the pharmaceutically acceptable diluent comprises Zn2+. In certain embodiments, the pharmaceutically acceptable diluent comprises aCSF. In certain embodiments, the total concentration of a divalent cation in the pharmaceutically acceptable diluent comprising aCSF is greater than 2.2 mM. In certain embodiments, the total concentration of a divalent cation is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the divalent cation is selected from Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or a combination thereof. In certain embodiments, the total concentration of Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or a combination thereof in the pharmaceutically acceptable diluent comprising aCSF is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Ca2+, Mg2+, or Zn2+, or a combination thereof in the pharmaceutically acceptable diluent comprising aCSF is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Ca2+or Mg2+, or a combination thereof in the pharmaceutically acceptable diluent comprising aCSF is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Ba2+in the pharmaceutically acceptable diluent comprising aCSF is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Be2+in the pharmaceutically acceptable diluent comprising aCSF is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Ca2+in the pharmaceutically acceptable diluent comprising aCSF is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Cu2+in the pharmaceutically acceptable diluent comprising aCSF is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Fe2+in the pharmaceutically acceptable diluent comprising aCSF is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Mg2+in the pharmaceutically acceptable diluent comprising aCSF is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Mn2+in the pharmaceutically acceptable diluent comprising aCSF is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Ni2+in the pharmaceutically acceptable diluent comprising aCSF is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Zn2+in the pharmaceutically acceptable diluent comprising aCSF is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of a divalent cation in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 40 mM. In certain embodiments, the total concentration of a divalent cation is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the divalent cation is selected from Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or a combination thereof. In certain embodiments, the total concentration of Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or a combination thereof in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of Ca2+, Mg2+, or Zn2+, or a combination thereof in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of Ca2+or Mg2+, or a combination thereof in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of Ba2+in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of Be2+in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of Ca2+in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of Cu2+in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of Fe2+in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of Mg2+in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of Mn2+in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of Ni2+in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of Zn2+in the pharmaceutically acceptable diluent comprising aCSF is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. III. Certain Molar Ratios of Divalent Cation to Oligomeric Compound Provided herein are pharmaceutical compositions comprising an oligomeric compound comprising a modified oligonucleotide, for example, a single-stranded oligonucleotide or a double-stranded oligonucleotide, and a pharmaceutically acceptable diluent comprising a divalent cation, in which the pharmaceutical composition ameliorates or prevents an acute neurotoxicity. In certain embodiments, the oligomeric compound is at a concentration of 1.2 mM or higher in the pharmaceutical composition. In certain embodiments, the oligomeric compound is at a concentration of 2 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 8 mM or higher, 10 mM or higher, 12 mM or higher, or 15 mM or higher. In certain embodiments, the oligomeric compound is at a concentration of 2 mM or higher. In certain embodiments, the oligomeric compound is at a concentration of 3 mM or higher. In certain embodiments, the oligomeric compound is at a concentration of 5 mM or higher. In certain embodiments, the oligomeric compound is at a concentration of 10 mM or higher. In all such embodiments, the divalent cation is at a molar ratio and / or concentration described herein. In certain embodiments, the oligomeric compound is at a concentration of from 2mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM. In certain embodiments, the oligomeric compound is at a concentration of from 2 mM to 15 mM. In certain embodiments, the oligomeric compound is at a concentration of from 2 mM to 10 mM. In certain embodiments, the oligomeric compound is at a concentration of from 2 mM to 5 mM. In certain embodiments, the oligomeric compound is at a concentration of from 5 mM to 20 mM. In certain embodiments, the oligomeric compound is at a concentration of from 5 mM to 15 mM. In certain embodiments, the oligomeric compound is at a concentration of from 10 mM to 20 mM. In certain embodiments, the oligomeric compound is at a concentration of from 10 mM to 15 mM. In all such embodiments, the divalent cation is at a molar ratio and / or concentration described herein. Provided herein are pharmaceutical compositions comprising an oligomeric compound comprising a modified oligonucleotide, for example, a single-stranded oligonucleotide or a double-stranded oligonucleotide, and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 5.2. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2.3 to 5.2. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2.3 to 3. In certain embodiments, the pharmaceutically acceptable diluent comprises a single divalent cation and the molar ratio is based on the total molar concentration of the single divalent cation in the pharmaceutical composition. In certain embodiments, the pharmaceutically acceptable diluent comprises a combination of divalent cations and the molar ratio is based on the total molar concentration of the combination of divalent cations in the pharmaceutical composition. In certain embodiments, the molar ratio is based on the total molar concentration of Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+, Mg2+, or Zn2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+or Mg2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ba2+. In certain embodiments, the molar ratio is based on the total molar concentration of Be2+. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+. In certain embodiments, the molar ratio is based on the total molar concentration of Cu2+. In certain embodiments, the molar ratio is based on the total molar concentration of Fe2+. In certain embodiments, the molar ratio is based on the total molar concentration of Mg2+. In certain embodiments, the molar ratio is based on the total molar concentration of Mn2+. In certain embodiments, the molar ratio is based on the total molar concentration of Ni2+. In certain embodiments, the molar ratio is based on the total molar concentration of Zn2+. In certain embodiments, the pharmaceutically acceptable diluent comprises aCSF. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 5.2. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2.3 to 5.2. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2.3 to 3. In certain embodiments, the pharmaceutically acceptable diluent comprising aCSF comprises Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or the total molar concentration of a combination thereof in the pharmaceutically acceptable diluent comprising aCSF. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+, Mg2+, or Zn2+, or the total molar concentration of a combination thereof in the pharmaceutically acceptable diluent comprising aCSF. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+or Mg2+, or the total molar concentration of a combination thereof in the pharmaceutically acceptable diluent comprising aCSF. In certain embodiments, the molar ratio is based on the total molar concentration of Ba2+in the pharmaceutically acceptable diluent comprising aCSF. In certain embodiments, the molar ratio is based on the total molar concentration of Be2+in the pharmaceutically acceptable diluent comprising aCSF. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+in the pharmaceutically acceptable diluent comprising aCSF. In certain embodiments, the molar ratio is based on the total molar concentration of Cu2+in the pharmaceutically acceptable diluent comprising aCSF. In certain embodiments, the molar ratio is based on the total molar concentration of Fe2+in the pharmaceutically acceptable diluent comprising aCSF. In certain embodiments, the molar ratio is based on the total molar concentration of Mg2+in the pharmaceutically acceptable diluent comprising aCSF. In certain embodiments, the molar ratio is based on the total molar concentration of Mn2+in the pharmaceutically acceptable diluent comprising aCSF. In certain embodiments, the molar ratio is based on the total molar concentration of Ni2+in the pharmaceutically acceptable diluent comprising aCSF. In certain embodiments, the molar ratio is based on the total molar concentration of Zn2+in the pharmaceutically acceptable diluent comprising aCSF. IV. Certain Pharmaceutical Compositions Provided herein are pharmaceutical compositions comprising an oligomeric compound comprising a modified oligonucleotide, for example, a single-stranded oligonucleotide or a double-stranded oligonucleotide, and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound is at a concentration of 1.2 mM or higher, and the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1. In certain embodiments, the oligomeric compound is at a concentration of 2 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 8 mM or higher, 10 mM or higher, 12 mM or higher, 15 mM or higher, or 20 mM or higher. In certain embodiments, the oligomeric compound is at a concentration of from 1.2 mM to 4 mM, from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiments, the pharmaceutically acceptable diluent comprises a single divalent cation and the molar ratio is based on the total molar concentration of the single divalent cation in the pharmaceutical composition. In certain embodiments, the pharmaceutically acceptable diluent comprises a combination of different divalent cations and the molar ratio is based on the total molar concentration of the combination of divalent cations in the pharmaceutical composition. In certain embodiments, the molar ratio is based on the total molar concentration of Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+, Mg2+, Fe2+, or Zn2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+or Mg2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+. In certain embodiments, the molar ratio is based on the total molar concentration of Mg2+. In certain embodiments, a divalent cation or a combination of different divalent cations chelate at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the backbone of the oligomeric compound. In certain embodiments, a divalent cation or a combination of different divalent cations fully chelate the backbone of the oligomeric compound. In certain embodiments, the pharmaceutically acceptable diluent comprises aCSF. In certain embodiments, the pharmaceutically acceptable diluent comprises PBS. Provided herein are pharmaceutical compositions comprising an oligomeric compound comprising a modified oligonucleotide, for example, a single-stranded oligonucleotide or a double-stranded oligonucleotide, and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. In certain embodiments, the oligomeric compound is at a concentration of 2 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 8 mM or higher, 10 mM or higher, 12 mM or higher, 15 mM or higher, or 20 mM or higher. In certain embodiments, the oligomeric compound is at a concentration of from 1.2 mM to 4 mM, from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM. In certain embodiments, the pharmaceutically acceptable diluent comprises a single divalent cation and the molar ratio is based on the total molar concentration of the single divalent cation in the pharmaceutical composition. In certain embodiments, the pharmaceutically acceptable diluent comprises a combination of different divalent cations and the molar ratio is based on the total molar concentration of the combination of divalent cations in the pharmaceutical composition. In certain embodiments, the molar ratio is based on the total molar concentration of Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+, Mg2+, Fe2+, or Zn2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+or Mg2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+. In certain embodiments, the molar ratio is based on the total molar concentration of Mg2+. In certain embodiments, a divalent cation or a combination of different divalent cations chelate at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the backbone of the oligomeric compound. In certain embodiments, a divalent cation or a combination of different divalent cations fully chelate the backbone of the oligomeric compound. In certain embodiments, the pharmaceutically acceptable diluent comprises aCSF. In certain embodiments, the pharmaceutically acceptable diluent comprises PBS. Provided herein are pharmaceutical compositions comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the total concentration of the divalent cation is greater than 2.2 mM. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1. In certain embodiments, the molar ratio of the divalent cation to the oligomeric compound is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. In certain embodiments, the total concentration of a divalent cation is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of a divalent cation is from 2.3 mM to 40 mM, from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the pharmaceutically acceptable diluent comprises a single divalent cation and the molar ratio is based on the total molar concentration of the single divalent cation in the pharmaceutical composition. In certain embodiments, the pharmaceutically acceptable diluent comprises a combination of different divalent cations and the molar ratio is based on the total molar concentration of the combination of divalent cations in the pharmaceutical composition. In certain embodiments, the molar ratio is based on the total molar concentration of Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+, Mg2+, Fe2+, or Zn2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+or Mg2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+. In certain embodiments, the molar ratio is based on the total molar concentration of Mg2+. In certain embodiments, a divalent cation or a combination of different divalent cations chelate at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the backbone of the oligomeric compound. In certain embodiments, a divalent cation or a combination of different divalent cations fully chelate the backbone of the oligomeric compound. In certain embodiments, the pharmaceutically acceptable diluent comprises aCSF. In certain embodiments, the pharmaceutically acceptable diluent comprises PBS. Provided herein are pharmaceutical compositions comprising an oligomeric compound and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 0.11*n to 0.37*n, wherein n is the number of anionic phosphate moieties in the modified oligonucleotide and * indicates multiplication. In certain embodiments, anionic phosphate moieties include ionizable free acid and / or anionic phosphodiester and phosphorothioate groups. In certain embodiments, n is the total number of P(V)-X-H moieties in a (free acid) oligomeric compound or oligomeric agent, where X is a heteroatom, optionally wherein X is selected from N, O, and S. In certain embodiments, n is the total number of phosphodiester, phosphorothioate, and phosphoramidate internucleoside linkages (e.g., linkage having formula Z4 as provided herein in which R1is H) in an oligomeric compound or oligomeric agent. In certain embodiments, n is the total number of phosphodiester, phosphorothioate, and mesyl phosphoramidate internucleoside linkages an oligomeric compound or oligomeric agent. In certain embodiments, n is the total number of phosphodiester and phosphorothioate internucleoside linkages in an oligomeric compound or oligomeric agent. In certain embodiments, the pharmaceutical composition comprises a single-stranded oligonucleotide and n is the total number of phosphodiester and phosphorothioate internucleoside linkages in the oligonucleotide. In certain embodiments, the pharmaceutical composition comprises a single-stranded oligonucleotide and n is the total number of phosphodiester, phosphorothioate, and phosphoramidate internucleoside linkages in the oligonucleotide. In certain embodiments, the pharmaceutical composition comprises an oligomeric duplex and n is the total number of phosphodiester and phosphorothioate internucleoside linkages in a first modified oligonucleotide and a second modified oligonucleotide. In certain embodiments, the molar ratio is from 0.12*n to 0.37*n, from 0.13*n to 0.37*n, from 0.15*n to 0.37*n, from 0.2*n to 0.37*n, from 0.3*n to 0.37*n, from 0.12*n to 0.3*n, from 0.12*n to 0.25*n, from 0.12*n to 0.27*n, from 0.15*n to 0.3*n, or from 0.2*n to 0.3*n. In certain embodiments, n is from 13 to 43, from 17 to 43, from 18 to 43, or from 19 to 43. In certain embodiments, n is 15, 16, 17, 18, 19, 20, 21, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, or 43. In certain embodiments, n is 15, 16, 17, 18, or 19. In certain embodiments, n is 17. In certain embodiments, n is 18. In certain embodiments, n is 19. In certain embodiments, the oligomeric compound is at a concentration of 1.2 mM or higher, 2 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 8 mM or higher, 10 mM or higher, 12 mM or higher, 15 mM or higher, or 20 mM or higher. In certain embodiments, the oligomeric compound is at a concentration of from 1.2 mM to 4 mM, from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM. In certain embodiments, the total concentration of a divalent cation is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of a divalent cation is from 2.3 mM to 40 mM, from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the pharmaceutically acceptable diluent comprises a single divalent cation and the molar ratio is based on the total molar concentration of the single divalent cation in the pharmaceutical composition. In certain embodiments, the pharmaceutically acceptable diluent comprises a combination of divalent cations and the molar ratio is based on the total molar concentration of the combination of divalent cations in the pharmaceutical composition. In certain embodiments, the molar ratio is based on the total molar concentration of Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+, Mg2+, or Zn2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+or Mg2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ba2+. In certain embodiments, the molar ratio is based on the total molar concentration of Be2+. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+. In certain embodiments, the molar ratio is based on the total molar concentration of Cu2+. In certain embodiments, the molar ratio is based on the total molar concentration of Fe2+. In certain embodiments, the molar ratio is based on the total molar concentration of Mg2+. In certain embodiments, the molar ratio is based on the total molar concentration of Mn2+. In certain embodiments, the molar ratio is based on the total molar concentration of Ni2+. In certain embodiments, the molar ratio is based on the total molar concentration of Zn2+. In certain embodiments, the pharmaceutically acceptable diluent comprises aCSF. In certain embodiments, the pharmaceutically acceptable diluent comprises PBS. In certain embodiments, the pharmaceutically acceptable diluent comprises aCSF. In certain embodiments, the pharmaceutical composition comprises an oligomeric compound and aCSF comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 0.11*n to 0.37*n. In certain embodiments, the molar ratio is from 0.12*n to 0.37*n, from 0.13*n to 0.37*n, from 0.15*n to 0.37*n, from 0.2*n to 0.37*n, from 0.3*n to 0.37*n, from 0.12*n to 0.3*n, from 0.12*n to 0.25*n, from 0.12*n to 0.27*n, from 0.15*n to 0.3*n, or from 0.2*n to 0.3*n. In certain embodiments, n is from 13 to 43, from 17 to 43, from 18 to 43, or from 19 to 43. In certain embodiments, n is 15, 16, 17, 18, 19, 20, 21, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, or 43. In certain embodiments, n is 15, 16, 17, 18, or 19. In certain embodiments, n is 17. In certain embodiments, n is 18. In certain embodiments, n is 19. In certain embodiments, the oligomeric compound is at a concentration of 1.2 mM or higher, 2 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 8 mM or higher, 10 mM or higher, 12 mM or higher, 15 mM or higher, or 20 mM or higher. In certain embodiments, the oligomeric compound is at a concentration of from 1.2 mM to 4 mM, from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM. In certain embodiments, the total concentration of a divalent cation is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of a divalent cation is from 2.3 mM to 40 mM, from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the pharmaceutically acceptable diluent comprises a single divalent cation and the molar ratio is based on the total molar concentration of the single divalent cation in the pharmaceutical composition. In certain embodiments, the pharmaceutically acceptable diluent comprises a combination of divalent cations and the molar ratio is based on the total molar concentration of the combination of divalent cations in the pharmaceutical composition. In certain embodiments, the molar ratio is based on the total molar concentration of Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, or Zn2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+, Mg2+, or Zn2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+or Mg2+, or the total molar concentration of a combination thereof. In certain embodiments, the molar ratio is based on the total molar concentration of Ba2+. In certain embodiments, the molar ratio is based on the total molar concentration of Be2+. In certain embodiments, the molar ratio is based on the total molar concentration of Ca2+. In certain embodiments, the molar ratio is based on the total molar concentration of Cu2+. In certain embodiments, the molar ratio is based on the total molar concentration of Fe2+. In certain embodiments, the molar ratio is based on the total molar concentration of Mg2+. In certain embodiments, the molar ratio is based on the total molar concentration of Mn2+. In certain embodiments, the molar ratio is based on the total molar concentration of Ni2+. In certain embodiments, the molar ratio is based on the total molar concentration of Zn2+. In certain embodiments, provided herein is a pharmaceutical composition comprising an oligomeric compound comprising a first modified oligonucleotide, and a second oligomeric compound comprising a second modified oligonucleotide, wherein the second oligomeric compound hybridizes to the oligomeric compound to form an oligomeric duplex and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric agent is from 0.11*n to 0.37*n, wherein n is the total number of anionic phosphate moieties in the first modified oligonucleotide and the second modified oligonucleotide. In certain embodiments, the molar ratio is from 0.12*n to 0.37*n, from 0.13*n to 0.37*n, from 0.15*n to 0.37*n, from 0.2*n to 0.37*n, from 0.3*n to 0.37*n, from 0.12*n to 0.3*n, from 0.12*n to 0.25*n, from 0.12*n to 0.27*n, from 0.15*n to 0.3*n, or from 0.2*n to 0.3*n. In certain embodiments, n is from 13 to 43, from 17 to 43, from 18 to 43, or from 19 to 43. In certain embodiments, n is 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, or 43. In certain embodiments, the second modified oligonucleotide consists of 12 to 30 linked nucleosides, and the nucleobase sequence of the second modified oligonucleotide comprises a complementary region of at least 8 nucleobases that is at least 90% complementary to an equal length portion of the first modified oligonucleotide. In certain embodiments, provided herein is a pharmaceutical composition comprising an oligomeric duplex comprising an antisense RNAi oligomeric compound comprising an antisense RNAi oligonucleotide and a sense RNAi oligomeric compound comprising a sense RNAi oligonucleotide, and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric agent is from 0.11*n to 0.37*n, wherein n is the total number of anionic phosphate moieties in the first modified oligonucleotide and the second modified oligonucleotide; wherein at least 10, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 nucleosides of the antisense RNAi oligonucleotide comprise a 2’-OMe sugar moiety, and wherein at least 10, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 nucleosides of the sense RNAi oligonucleotide comprise a 2’-OMe sugar moiety. In certain such embodiments the remainder of the nucleosides in the oligomeric duplex are selected from 2’- deoxynucleosides, 2’-F nucleosides, and 2’-MOE nucleosides. In certain embodiments, the antisense RNAi oligonucleotide comprises exactly 1, 2, 3, 4, or 5 nucleosides comprising a 2’-F sugar moiety. In certain embodiments, the sense RNAi oligonucleotide comprises exactly 1, 2, 3, 4, or 5 nucleosides comprising a 2’- F sugar moiety. In certain embodiments, the antisense RNAi oligonucleotide comprises a 2’-F nucleoside at one or two of nucleosides 2 and / or 14, counting from the 5’-terminal nucleoside thereof. In certain embodiments, the sense RNAi oligonucleotide comprises a 2’-F nucleoside at one, two, three or four of nucleosides 7, 9, 10, and / or 11, counting from the 5’-terminal nucleoside thereof. In certain embodiments, the molar ratio is from 0.12*n to 0.37*n, from 0.13*n to 0.37*n, from 0.15*n to 0.37*n, from 0.2*n to 0.37*n, from 0.3*n to 0.37*n, from 0.12*n to 0.3*n, from 0.12*n to 0.25*n, from 0.12*n to 0.27*n, from 0.15*n to 0.3*n, or from 0.2*n to 0.3*n. In certain embodiments, n is from 13 to 43, from 17 to 43, from 18 to 43, or from 19 to 43. In certain embodiments, n is 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, or 43. In certain embodiments, the second modified oligonucleotide consists of 12 to 30 linked nucleosides, and the nucleobase sequence of the second modified oligonucleotide comprises a complementary region of at least 8 nucleobases that is at least 90% complementary to an equal length portion of the first modified oligonucleotide. A. Exemplary Pharmaceutical Compositions In certain embodiments, a pharmaceutical composition described herein comprises an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising Mg2+(e.g., from MgCl2), Ca2+(e.g., from CaCl2), or a combination thereof, wherein the oligomeric compound is at a concentration of 1.2 mM or higher, and the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric compound is from 2 to 7.1. In certain embodiments, the oligomeric compound is at a concentration of 2 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 8 mM or higher, 10 mM or higher, 12 mM or higher, 15 mM or higher, or 20 mM or higher. In certain embodiments, the oligomeric compound is at a concentration of from 1.2 mM to 4 mM, from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM. In certain embodiments, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric compound is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiment, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric compound is from 2.3 to 5.2. In certain embodiments, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric compound is from 2 to 3. In certain embodiments, the pharmaceutically acceptable diluent comprises aCSF. In certain embodiments, the pharmaceutically acceptable diluent comprises PBS. In certain embodiments, the pharmaceutical composition consists essentially of or consists of the oligomeric compound and aCSF consisting of Mg2+(e.g., from MgCl2), Ca2+(e.g., from CaCl2), or a combination thereof. In certain embodiments, the pharmaceutical composition consists essentially of or consists of the oligomeric compound and PBS consisting of Mg2+(e.g., from MgCl2), Ca2+(e.g., from CaCl2), or a combination thereof. In certain embodiments, a pharmaceutical composition described herein comprises an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising Mg2+(e.g., from MgCl2), Ca2+(e.g., from CaCl2), or a combination thereof, wherein the total concentration of Mg2+, Ca2+, or a combination thereof is greater than 2.2 mM. In certain embodiments, the total concentration of Mg2+, Ca2+, or a combination thereof is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Mg2+, Ca2+, or a combination thereof is from 2.3 mM to 40 mM, from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric compound is from 2 to 7.1. In certain embodiments, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric compound is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiment, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric compound is from 2.3 to 5.2. In certain embodiments, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric compound is from 2 to 3. In certain embodiments, the pharmaceutically acceptable diluent comprises aCSF. In certain embodiments, the pharmaceutically acceptable diluent comprises PBS. In certain embodiments, the pharmaceutical composition consists essentially of or consists of the oligomeric compound and aCSF consisting of Mg2+(e.g., from MgCl2), Ca2+(e.g., from CaCl2), or a combination thereof. In certain embodiments, the pharmaceutical composition consists essentially of or consists of the oligomeric compound and PBS consisting of Mg2+(e.g., from MgCl2), Ca2+(e.g., from CaCl2), or a combination thereof. In certain embodiments, a pharmaceutical composition described herein comprises an oligomeric compound comprising a modified oligonucleotide and aCSF supplemented with additional MgCl2, wherein the oligomeric compound is at a concentration of 1.2 mM or higher, and the molar ratio of divalent cation (total molar concentration of Mg2+and Ca2+in aCSF) to the oligomeric compound is from 2 to 7.1. In certain embodiments, the oligomeric compound is at a concentration of 2 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 8 mM or higher, 10 mM or higher, 12 mM or higher, 15 mM or higher, or 20 mM or higher. In certain embodiments, the oligomeric compound is at a concentration of from 1.2 mM to 4 mM, from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiment, the molar ratio of divalent cation to the oligomeric compound is from 2.3 to 5.2. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. In certain embodiments, a pharmaceutical composition described herein comprises an oligomeric compound comprising a modified oligonucleotide and aCSF supplemented with additional MgCl2, wherein the total concentration of divalent cation (total molar concentration of Mg2+and Ca2+in aCSF) is greater than 2.2 mM. In certain embodiments, the total concentration of divalent cation is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of divalent cation is from 2.3 mM to 40 mM, from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiment, the molar ratio of divalent cation to the oligomeric compound is from 2.3 to 5.2. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. In certain embodiments, a pharmaceutical composition described herein comprises an oligomeric compound comprising a modified oligonucleotide and aCSF supplemented with additional CaCl2, wherein the oligomeric compound is at a concentration of 1.2 mM or higher, and the molar ratio of divalent cation (total molar concentration of Mg2+and Ca2+in aCSF) to the oligomeric compound is from 2 to 7.1. In certain embodiments, the oligomeric compound is at a concentration of 2 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 8 mM or higher, 10 mM or higher, 12 mM or higher, 15 mM or higher, or 20 mM or higher. In certain embodiments, the oligomeric compound is at a concentration of from 1.2 mM to 4 mM, from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiment, the molar ratio of divalent cation to the oligomeric compound is from 2.3 to 5.2. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. In certain embodiments, a pharmaceutical composition described herein comprises an oligomeric compound comprising a modified oligonucleotide and aCSF supplemented with additional CaCl2, wherein the total concentration of divalent cation (total molar concentration of Mg2+and Ca2+in aCSF) is greater than 2.2 mM. In certain embodiments, the total concentration of divalent cation is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of divalent cation is from 2.3 mM to 40 mM, from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiment, the molar ratio of divalent cation to the oligomeric compound is from 2.3 to 5.2. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. In certain embodiments, a pharmaceutical composition described herein comprises an oligomeric duplex and a pharmaceutically acceptable diluent comprising Mg2+(e.g., from MgCl2), Ca2+(e.g., from CaCl2), or a combination thereof, wherein the oligomeric duplex is at a concentration of 1.2 mM or higher, and the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric duplex is from 2 to 7.1. In certain embodiments, the oligomeric duplex is at a concentration of 2 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 8 mM or higher, 10 mM or higher, 12 mM or higher, 15 mM or higher, or 20 mM or higher. In certain embodiments, the oligomeric duplex is at a concentration of from 1.2 mM to 4 mM, from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM. In certain embodiments, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric duplex is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiment, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric duplex is from 2.3 to 5.2. In certain embodiments, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric duplex is from 2 to 3. In certain embodiments, each oligomeric compound of the oligomeric duplex comprises a modified oligonucleotide. In certain embodiments, the oligomeric duplex is an RNAi agent. In certain embodiments, the pharmaceutically acceptable diluent comprises aCSF. In certain embodiments, the pharmaceutically acceptable diluent comprises PBS. In certain embodiments, a pharmaceutical composition described herein comprises an oligomeric duplex and a pharmaceutically acceptable diluent comprising Mg2+(e.g., from MgCl2), Ca2+(e.g., from CaCl2), or a combination thereof, wherein the total concentration of Mg2+, Ca2+, or a combination thereof is greater than 2.2 mM. In certain embodiments, the total concentration of Mg2+, Ca2+, or a combination thereof is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of Mg2+, Ca2+, or a combination thereof is from 2.3 mM to 40 mM, from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of Mg2+, Ca2+, or a combination thereof is lower than 10 mM, lower than 8 mM, lower than 5 mM, or lower than 3 mM. In certain embodiments, the total concentration of Mg2+, Ca2+, or a combination thereof is greater than 2.2 mM but lower than 10 mM. In certain embodiments, the total concentration of Mg2+, Ca2+, or a combination thereof is from 2.3 mM to 10 mM. In certain embodiments, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric duplex is from 2 to 7.1. In certain embodiments, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric duplex is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiment, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric duplex is from 2.3 to 5.2. In certain embodiments, the molar ratio of Mg2+, Ca2+, or a combination thereof to the oligomeric duplex is from 2 to 3. In certain embodiments, each oligomeric compound of the oligomeric duplex comprises a modified oligonucleotide. In certain embodiments, the oligomeric duplex is an RNAi agent. In certain embodiments, the pharmaceutically acceptable diluent comprises aCSF. In certain embodiments, the pharmaceutically acceptable diluent comprises PBS. In certain embodiments, the pharmaceutical composition consists essentially of or consists of the oligomeric duplex and aCSF consisting of Mg2+(e.g., from MgCl2), Ca2+(e.g., from CaCl2), or a combination thereof. In certain embodiments, the pharmaceutical composition consists essentially of or consists of the oligomeric duplex and PBS consisting of Mg2+(e.g., from MgCl2), Ca2+(e.g., from CaCl2), or a combination thereof. In certain embodiments, a pharmaceutical composition described herein comprises an oligomeric duplex and aCSF supplemented with additional MgCl2, wherein the oligomeric duplex is at a concentration of 1.2 mM or higher, and the molar ratio of divalent cation (total molar concentration of Mg2+and Ca2+in aCSF) to the oligomeric duplex is from 2 to 16. In certain embodiments, the oligomeric duplex is at a concentration of 2 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 8 mM or higher, 10 mM or higher, 12 mM or higher, 15 mM or higher, or 20 mM or higher. In certain embodiments, the oligomeric duplex is at a concentration of from 1.2 mM to 4 mM, from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM. In certain embodiments, the molar ratio is from 2 to 7.1, from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiment, the molar ratio of divalent cation to the oligomeric duplex is from 2.3 to 5.2. In certain embodiments, the molar ratio of divalent cation to the oligomeric duplex is from 2 to 3. In certain embodiments, each oligomeric compound of the oligomeric duplex comprises a modified oligonucleotide. In certain embodiments, the oligomeric duplex is an RNAi agent. In certain embodiments, a pharmaceutical composition described herein comprises an oligomeric duplex and aCSF supplemented with additional MgCl2, wherein the total concentration of divalent cation (total molar concentration of Mg2+and Ca2+in aCSF) is greater than 2.2 mM. In certain embodiments, the total concentration of divalent cation is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of divalent cation is from 2.3 mM to 40 mM, from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of divalent cation is lower than 10 mM, lower than 8 mM, lower than 5 mM, or lower than 3 mM. In certain embodiments, the total concentration of divalent cation is greater than 2.2 mM but lower than 10 mM. In certain embodiments, the total concentration of divalent cation is from 2.3 mM to 10 mM. In certain embodiments, the molar ratio of divalent cation to the oligomeric duplex is from 2 to 7.1, from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiment, the molar ratio of divalent cation to the oligomeric duplex is from 2.3 to 5.2. In certain embodiments, the molar ratio of divalent cation to the oligomeric duplex is from 2 to 3. In certain embodiments, each oligomeric compound of the oligomeric duplex comprises a modified oligonucleotide. In certain embodiments, the oligomeric duplex is an RNAi agent. In certain embodiments, a pharmaceutical composition described herein comprises an oligomeric duplex and aCSF supplemented with additional CaCl2, wherein the oligomeric duplex is at a concentration of 1.2 mM or higher, and the molar ratio of divalent cation (total molar concentration of Mg2+and Ca2+in aCSF) to the oligomeric duplex is from 2 to 7.1. In certain embodiments, the oligomeric duplex is at a concentration of 2 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 8 mM or higher, 10 mM or higher, 12 mM or higher, 15 mM or higher, or 20 mM or higher. In certain embodiments, the oligomeric duplex is at a concentration of from 1.2 mM to 4 mM, from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM. In certain embodiments, the molar ratio is from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiment, the molar ratio of divalent cation to the oligomeric duplex is from 2.3 to 5.2. In certain embodiments, the molar ratio of divalent cation to the oligomeric duplex is from 2 to 3. In certain embodiments, each oligomeric compound of the oligomeric duplex comprises a modified oligonucleotide. In certain embodiments, the oligomeric duplex is an RNAi agent. In certain embodiments, a pharmaceutical composition described herein comprises an oligomeric duplex and aCSF supplemented with additional CaCl2, wherein the total concentration of divalent cation (total molar concentration of Mg2+and Ca2+in aCSF) is greater than 2.2 mM. In certain embodiments, the total concentration of divalent cation is 2.3 mM or higher, 2.4 mM or higher, 2.5 mM or higher, 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, 15 mM or higher, 20 mM or higher, 25 mM or higher, 30 mM or higher, or 35 mM or higher. In certain embodiments, the total concentration of divalent cation is from 2.3 mM to 40 mM, from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 35 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 35 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 35 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 35 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, from 15 mM to 35 mM, or from 15 mM to 30 mM. In certain embodiments, the total concentration of divalent cation is lower than 10 mM, lower than 8 mM, lower than 5 mM, or lower than 3 mM. In certain embodiments, the total concentration of divalent cation is greater than 2.2 mM but lower than 10 mM. In certain embodiments, the total concentration of divalent cation is from 2.3 mM to 10 mM. In certain embodiments, the molar ratio is from 2 to 7.1, from 2 to 6, from 2 to 5.2, from 2 to 5, from 2 to 4, from 2 to 3, from 2.3 to 7, from 2.3 to 5.2, from 2.3 to 5, from 2.3 to 3, from 3 to 7, from 3 to 6, from 3 to 5.2, from 3 to 5, or from 4 to 6. In certain embodiment, the molar ratio of divalent cation to the oligomeric duplex is from 2.3 to 5.2. In certain embodiments, the molar ratio of divalent cation to the oligomeric duplex is from 2 to 3. In certain embodiments, each oligomeric compound of the oligomeric duplex comprises a modified oligonucleotide. In certain embodiments, the oligomeric duplex is an RNAi agent. In certain embodiments, provided is a pharmaceutical composition comprising an oligomeric compound comprising a single stranded modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1, wherein the modified oligonucleotide comprises a 5’-region consisting of 1-6 linked 5’-region nucleosides, a 3’-region consisting of 1-6 linked 3’-region nucleosides, and a central deoxy region consisting of 6-10 linked 2’-β-D- deoxynucleosides, and wherein each 5’-region nucleoside and each 3’-region nucleoside comprises a sugar moiety selected from a cEt sugar moiety, an LNA sugar moiety, a 2’-MOE sugar moiety, and a 2’-OMe sugar moiety. In certain embodiments, each internucleoside linkage is selected from a phosphodiester, phosphorothioate, and a mesyl phosphoramidate. In certain embodiments, the concentration of the oligomeric compound is 1.2 mM or higher. In certain embodiments, the divalent cation is selected from Ca2+, Mg2+, or a combination thereof. In certain embodiments, provided is a pharmaceutical composition comprising an oligomeric compound comprising a single stranded modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1, wherein the modified oligonucleotide consists of 15-20 linked nucleosides, wherein each nucleoside comprises a sugar moiety selected from a cEt sugar moiety, an LNA sugar moiety, a 2’-MOE sugar moiety, a 2’-OMe sugar moiety, and a 2’-NMA sugar moiety. In certain embodiments, each internucleoside linkage is selected from a phosphodiester, phosphorothioate, and a mesyl phosphoramidate. In certain embodiments, at least 80% of the nucleosides of the modified oligonucleotide comprise a 2’-MOE sugar or a 2’-NMA sugar moiety. In certain embodiments, the concentration of the oligomeric compound is 1.2 mM or higher. In certain embodiments, the divalent cation is selected from Ca2+, Mg2+, or a combination thereof. In certain embodiments, provided is a pharmaceutical composition comprising an oligomeric compound comprising a single-stranded modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the total concentration of the divalent cation is greater than 2.2 mM. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. In certain embodiments, provided is a pharmaceutical composition comprising an oligomeric compound comprising a single-stranded modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. In certain embodiments, provided is a pharmaceutical composition comprising an oligomeric compound comprising a single-stranded modified oligonucleotide and artificial cerebrospinal fluid (aCSF) comprising an excess of a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound to from 2 to 7.1. B. Additional Pharmaceutical Formulation Components In certain embodiments, the pharmaceutical composition comprises one or more additional formulation components. For example, oligomeric compounds and / or oligomeric duplexes described herein may be admixed with pharmaceutically acceptable active and / or inert substances for the preparation of pharmaceutical compositions or formulations. Compositions and methods for the formulation of pharmaceutical compositions depend on a number of criteria, including, but not limited to, route of administration, extent of disease, or dose to be administered. In certain embodiments, pharmaceutical compositions disclosed herein comprise one or more excipients. In certain embodiments, excipients are selected from water, salt solutions, alcohol, polyethylene glycols, gelatin, lactose, amylase, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, and polyvinylpyrrolidone. In certain embodiments, pharmaceutical compositions disclosed herein comprise a delivery system. Examples of delivery systems include, but are not limited to, liposomes, emulsions, and viral vector delivery systems. Certain delivery systems are useful for preparing certain pharmaceutical compositions including those comprising hydrophobic compounds. In certain embodiments, certain organic solvents such as dimethylsulfoxide are used. In certain embodiments, pharmaceutical compositions comprise one or more tissue-specific delivery molecules designed to deliver the oligomeric compounds and / or oligomeric duplexes described herein to specific tissues or cell types. For example, in certain embodiments, pharmaceutical compositions include liposomes coated with a tissue-specific antibody. In certain embodiments, pharmaceutical compositions comprise a co-solvent system. Certain of such co-solvent systems comprise, for example, benzyl alcohol, a nonpolar surfactant, a water-miscible organic polymer, and an aqueous phase. In certain embodiments, such co-solvent systems are used for hydrophobic compounds. A non-limiting example of such a co-solvent system is the VPD co-solvent system, which is a solution of absolute ethanol comprising 3% w / v benzyl alcohol, 8% w / v of the nonpolar surfactant Polysorbate 80™ and 65% w / v polyethylene glycol 300. The proportions of such co-solvent systems may be varied considerably without significantly altering their solubility and toxicity characteristics. Furthermore, the identity of co-solvent components may be varied: for example, other surfactants may be used instead of Polysorbate 80™; the fraction size of polyethylene glycol may be varied; other biocompatible polymers may replace polyethylene glycol, e.g., polyvinyl pyrrolidone; and other sugars or polysaccharides may substitute for dextrose. In certain embodiments, pharmaceutical compositions described herein are prepared for administration by injection (e.g., intravenous, subcutaneous, intramuscular, intrathecal (IT), intracerebroventricular (ICV), etc.). In certain of such embodiments, a pharmaceutical composition comprises a carrier and is formulated in aqueous solution, such as water or physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer. In certain embodiments, other ingredients are included (e.g., ingredients that aid in solubility or serve as preservatives). In certain embodiments, injectable suspensions are prepared using appropriate liquid carriers, suspending agents and the like. Certain pharmaceutical compositions for injection are presented in unit dosage form, e.g., in ampoules or in multi- dose containers. Certain pharmaceutical compositions for injection are suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or dispersing agents. Certain solvents suitable for use in pharmaceutical compositions for injection include, but are not limited to, lipophilic solvents and fatty oils, such as sesame oil, synthetic fatty acid esters, such as ethyl oleate or triglycerides, and liposomes. V. Certain Oligonucleotides In certain embodiments, oligomeric compounds comprise oligonucleotides, which consists of linked nucleosides. Oligonucleotides may be unmodified oligonucleotides (RNA or DNA) or may be modified oligonucleotides. Modified oligonucleotides comprise at least one modification relative to unmodified RNA or DNA. That is, modified oligonucleotides comprise at least one modified nucleoside (comprising a modified sugar moiety and / or a modified nucleobase) and / or at least one modified internucleoside linkage. Certain modified nucleosides and modified internucleoside linkages suitable for use in modified oligonucleotides are described below. A. Certain Modified Nucleosides Modified nucleosides comprise a modified sugar moiety or a modified nucleobase or both a modified sugar moiety and a modified nucleobase. In certain embodiments, modified nucleosides comprising the following modified sugar moieties and / or the following modified nucleobases may be incorporated into oligonucleotides. 1. Certain Sugar Moieties In certain embodiments, modified sugar moieties are non-bicyclic modified sugar moieties. In certain embodiments, modified sugar moieties are bicyclic or tricyclic sugar moieties. In certain embodiments, modified sugar moieties are sugar surrogates. Such sugar surrogates may comprise one or more substitutions corresponding to those of other types of modified sugar moieties. In certain embodiments, modified sugar moieties are non-bicyclic modified furanosyl sugar moieties comprising one or more acyclic substituent, including, but not limited to, substituents at the 2’, 3’, 4’, and / or 5’ positions. In certain embodiments, the furanosyl sugar moiety is a ribosyl sugar moiety. In certain embodiments, one or more acyclic substituent of non-bicyclic modified sugar moieties is branched. In certain embodiments, non-bicyclic modifed sugar moieties comprise a substituent group at the 2’- position. Examples of substituent groups suitable for the 2’-position of modified sugar moieties include but are not limited to: -F, -OCH3(“OMe” or “O-methyl”), and -OCH2CH2OCH3(“MOE”). In certain embodiments, 2’-substituent groups are selected from: halo, allyl, amino, azido, SH, CN, OCN, CF3, OCF3, O-C1-C10alkoxy, O-C1-C10substituted alkoxy, O-C1-C10alkyl, O-C1-C10substituted alkyl, S-alkyl, N(Rm)- alkyl, O-alkenyl, S-alkenyl, N(Rm)-alkenyl, O-alkynyl, S-alkynyl, N(Rm)-alkynyl, O-alkylenyl-O-alkyl, alkynyl, alkaryl, aralkyl, O-alkaryl, O-aralkyl, O(CH2)2SCH3, O(CH2)2ON(Rm)(Rn) or OCH2C(=O)- N(Rm)(Rn), where each Rmand Rnis, independently, H, an amino protecting group, or substituted or unsubstituted C1-C10alkyl, -O(CH2)2ON(CH3)2(“DMAOE”), or 2’-O(CH2)2O(CH2)2N(CH3)2(“DMAEOE”). And the 2’-substituent groups described in Cook et al., U.S.6,531,584; Cook et al., U.S.5,859,221; and Cook et al., U.S.6,005,087 Synthetic methods for some of these 2’-substituent groups can be found in ,e.g., Cook et al., U.S. 6,531,584; and Cook et al., U.S.5,859,221. Certain embodiments of these 2’-substituent groups can be further substituted with one or more substituent groups independently selected from: hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro (NO2), thiol, thioalkoxy, thioalkyl, halogen, alkyl, aryl, alkenyl and alkynyl. In certain embodiments, a 2’-substituted non-bicyclic modified nucleoside comprises a sugar moiety comprising a non-bridging 2’-substituent group selected from: F, NH2, N3, OCF3,OCH3, O(CH2)3NH2, CH2CH=CH2, OCH2CH=CH2, OCH2CH2OCH3, O(CH2)2SCH3, O(CH2)2ON(Rm)(Rn), O(CH2)2O(CH2)2N(CH3)2, and N-substituted acetamide (OCH2C(=O)-N(Rm)(Rn)), where each Rmand Rnis, independently, H, an amino protecting group, or substituted or unsubstituted C1-C10alkyl. In certain embodiments, a 2’-substituted sugar moiety of a modified nucleoside comprises 2’- substituent group selected from: F, OCF3,OCH3, OCH2CH2OCH3, O(CH2)2SCH3, O(CH2)2ON(CH3)2, O(CH2)2O(CH2)2N(CH3)2, O(CH2)2ON(CH3)2(“DMAOE”), O(CH2)2O(CH2)2N(CH3)2(“DMAEOE”), and OCH2C(=O)-N(H)CH3(“NMA”). In certain embodiments, a 2’-substituted non-bicyclic modified nucleoside comprises a sugar moiety comprising a non-bridging 2’-substituent group selected from: F, OCH3, OCH2CH2OCH3, O(CH2)2SCH3, O(CH2)2ON(CH3)2, O(CH2)2O(CH2)2N(CH3)2, and OCH2C(=O)-N(H)CH3(“NMA”). In certain embodiments, a 2’-substituted sugar moiety of a modified nucleoside comprises 2’- substituent group selected from: F, OCH3, and OCH2CH2OCH3. In certain embodiments, modified furanosyl sugar moieties and nucleosides incorporating such modified furanosyl sugar moieties are further defined by isomeric configuration. For example, a 2’- deoxyfuranosyl sugar moiety may be in seven isomeric configurations other than the naturally occurring β-D- deoxyribosyl configuration. Such modified sugar moieties are described in, e.g., WO2020 / 072991. A 2’- modified sugar moiety has an additional stereocenter at the 2’-position relative to a 2’-deoxyfuranosyl sugar moiety; therefore, such sugar moieties have a total of sixteen possible isomeric configurations. Modified furanosyl sugar moieties described herein are in the β-D-ribosyl isomeric configuration unless otherwise specified. In certain embodiments, non-bicyclic modified sugar moieties are stereoisomers of DNA, such as 2’- β-D-deoxyxylosyl sugar moiety: . a non-bicyclic modified nucleoside comprises a 2’-α-L-deoxyribosyl sugar moiety: . non-bicyclic modified sugar moieties comprise a substituent group at the 4’- position. Examples of substituent groups suitable for the 4’-position of modified sugar moieties include, but are not limited to, alkoxy (e.g., methoxy), alkyl, and those described in Manoharan et al., WO 2015 / 106128. In certain embodiments, non-bicyclic modified sugar moieties comprise a substituent group at the 3’- position. Examples of substituent groups suitable for the 3’-position of modified sugar moieties include, but are not limited to, alkoxy (e.g., methoxy), and alkyl (e.g., methyl, ethyl). In certain embodiments, non-bicyclic modified sugar moieties comprise a substituent group at the 5’- position. Examples of substituent groups suitable for the 5’-position of modified sugar moieties include, but are not limited to, vinyl, alkoxy (e.g., methoxy), and alkyl (e.g., methyl (R or S), ethyl). In certain embodiments, non-bicyclic modified sugar moieties comprise more than one non-bridging sugar substituent, for example, 2’-F-5’-methyl sugar moieties, such as described in Migawa et al., US2010 / 0190837, or alternative 2’- and 5’-modified sugar moieties as described in Rajeev et al., US2013 / 0203836. In naturally occurring nucleic acids, sugars are linked to one another 3’ to 5’. In certain embodiments, oligonucleotides include one or more nucleoside or sugar moiety linked at an alternative position, for example at the 2’ position or inverted 5’ to 3’. For example, where the linkage is at the 2’ position, the 2’-substituent groups may instead be at the 3’-position. Certain modified sugar moieties comprise a substituent that bridges two atoms of the furanosyl ring to form a second ring, resulting in a bicyclic sugar moiety. In certain embodiments, the bicyclic sugar moiety comprises a bridge between the 4’ and the 2’ furanose ring atoms. Examples of such 4’ to 2’ bridging sugar substituents include, but are not limited to: 4’-CH2-2’, 4’-(CH2)2-2’, 4’-(CH2)3-2’, 4’-CH2-O-2’ (“LNA”), 4’- CH2-S-2’, 4’-(CH2)2-O-2’ (“ENA”), 4’-CH(CH3)-O-2’ (referred to as “constrained ethyl” or “cEt” when in the S configuration), 4’-CH2-O-CH2-2’, 4’-CH2-N(R)-2’, 4’-CH(CH2OCH3)-O-2’ (“constrained MOE” or “cMOE”) and analogs thereof, 4’-C(CH3)(CH3)-O-2’ and analogs thereof, 4’-CH2-N(OCH3)-2’ and analogs thereof , 4’-CH2-O-N(CH3)-2’ , 4’-CH2-C(H)(CH3)-2’, 4’-CH2-C(=CH2)-2’ and analogs thereof ), 4’-C(RaRb)-N(R)-O-2’, 4’-C(RaRb)-O-N(R)-2’, 4’-CH2-O-N(R)-2’, and 4’-CH2-N(R)-O-2’, wherein each R, Ra, and Rbis, independently, H, a protecting group, or C1-C12alkyl. Representative U.S. patents that teach the preparation of such bicyclic sugar moieties include, but are not limited to: Imanishi et al., U.S.7,427,672; Swayze et al., U.S.7,741,457, and Swayze et al., U.S.8,022,193; Seth et al., U.S.8,278,283; Prakash et al., U.S.8,278,425; Seth et al., U.S.8,278,426). In certain embodiments, such 4’ to 2’ bridges independently comprise from 1 to 4 linked groups independently selected from: -[C(Ra)(Rb)]n-, -[C(Ra)(Rb)]n-O-, -C(Ra)=C(Rb)-, -C(Ra)=N-, -C(=NRa)-, - C(=O)-, -C(=S)-, -O-, -Si(Ra)2-, -S(=O)x-, and -N(Ra)-; wherein: x is 0, 1, or 2; n is 1, 2, 3, or 4; each Raand Rbis, independently, H, a protecting group, hydroxyl, C1-C12alkyl, substituted C1-C12alkyl, C2-C12alkenyl, substituted C2-C12alkenyl, C2-C12alkynyl, substituted C2-C12alkynyl, C5-C20aryl, substituted C5-C20aryl, heterocycle radical, substituted heterocycle radical, heteroaryl, substituted heteroaryl, C5-C7alicyclic radical, substituted C5-C7alicyclic radical, halogen, OJ1, NJ1J2, SJ1, N3, COOJ1, acyl (C(=O)- H), substituted acyl, CN, sulfonyl (S(=O)2-J1), or sulfoxyl (S(=O)-J1); and each J1and J2is, independently, H, C1-C12alkyl, substituted C1-C12alkyl, C2-C12alkenyl, substituted C2-C12alkenyl, C2-C12alkynyl, substituted C2-C12alkynyl, C5-C20aryl, substituted C5-C20aryl, acyl (C(=O)-H), substituted acyl, a heterocycle radical, a substituted heterocycle radical, C1-C12aminoalkyl, substituted C1-C12aminoalkyl, or a protecting group. Additional bicyclic sugar moieties are known in the art, see, for example: Wan, et al., J. Medicinal Chemistry, 2016, 59, 9645-9667; Wengel et al., U.S.8,080,644; Ramasamy et al., U.S.6,525,191; Seth et al., U.S.7,547,684; and Seth et al., U.S.7,666,854. In certain embodiments, bicyclic sugar moieties and nucleosides incorporating such bicyclic sugar moieties are further defined by isomeric configuration. For example, an LNA nucleoside (described herein) may be in the α-L configuration or in the β-D configuration. α-L-methyleneoxy (4’-CH2-O-2’) or α-L-LNA bicyclic nucleosides have been incorporated into oligonucleotides that showed antisense activity (Frieden et al., Nucleic Acids Research, 2003, 21, 6365- 6372). The addition of locked nucleic acids to siRNAs has been shown to increase siRNA stability in serum, and to reduce off-target effects (Elmen, J. et al., (2005) Nucleic Acids Research 33(1):439-447; Mook, OR. et al., (2007) Mol Canc Ther 6(3):833-843; Grunweller, A. et al., (2003) Nucleic Acids Research 31(12):3185- 3193). Herein, general descriptions of bicyclic nucleosides include both isomeric configurations. When the positions of specific bicyclic nucleosides (e.g., LNA or cEt) are identified in exemplified embodiments herein, they are in the β-D configuration, unless otherwise specified. In certain embodiments, modified sugar moieties comprise one or more non-bridging sugar substituent and one or more bridging sugar substituent (e.g., 5’-substituted and 4’-2’ bridged sugars). In certain embodiments, modified sugar moieties are sugar surrogates. In certain such embodiments, the oxygen atom of the sugar moiety is replaced, e.g., with a sulfur, carbon or nitrogen atom. In certain such embodiments, such modified sugar moieties also comprise bridging and / or non-bridging substituents as described herein. For example, certain sugar surrogates comprise a 4’-sulfur atom and a substitution at the 2'- position and / or the 5’ position. In certain embodiments, sugar surrogates comprise rings having other than 5 atoms. For example, in certain embodiments, a sugar surrogate comprises a six-membered tetrahydropyran (“THP”). Such tetrahydropyrans may be further modified or substituted. Nucleosides comprising such modified tetrahydropyrans include, but are not limited to, hexitol nucleic acid (“HNA”), anitol nucleic acid (“ANA”), manitol nucleic acid (“MNA”), fluoro HNA: (“F-HNA”, see e.g., Egli, et. al., J Am Chem (2011) 133(41):16642-16649, Swayze et al., U.S.8,088,904; and Swayze et al., U.S.8,440,803) F-HNA can also be referred to as a F-THP or 3'-fluoro tetrahydropyran, and nucleosides comprising additional modified THP compounds having the formula: wherein, independently, for each of said modified THP nucleoside: Bx is a nucleobase moiety; T3and T4are each, independently, an internucleoside linking group linking the modified THP nucleoside to the remainder of an oligonucleotide or one of T3and T4is an internucleoside linking group linking the modified THP nucleoside to the remainder of an oligonucleotide and the other of T3and T4is H, a hydroxyl protecting group, a linked conjugate group, or a 5' or 3'-terminal group; q1, q2, q3, q4, q5, q6and q7are each, independently, H, C1-C6alkyl, substituted C1-C6alkyl, C2-C6alkenyl, substituted C2-C6alkenyl, C2- C6alkynyl, or substituted C2-C6alkynyl; and each of R1and R2is independently selected from: hydrogen, halogen, substituted or unsubstituted alkoxy, NJ1J2, SJ1, N3, OC(=X)J1, OC(=X)NJ1J2, NJ3C(=X)NJ1J2, and CN, wherein X is O, S or NJ1, and each J1, J2, and J3is, independently, H or C1-C6alkyl. In certain embodiments, modified THP nucleosides are provided wherein q1, q2, q3, q4, q5, q6and q7are each H. In certain embodiments, at least one of q1, q2, q3, q4, q5, q6and q7is other than H. In certain embodiments, at least one of q1, q2, q3, q4, q5, q6and q7is methyl. In certain embodiments, modified THP nucleosides are provided wherein one of R1and R2is F. In certain embodiments, R1is F and R2is H, in certain embodiments, R1is methoxy and R2is H, and in certain embodiments, R1is methoxyethoxy and R2is H. In certain embodiments, sugar surrogates comprise rings having more than 5 atoms and more than one heteroatom. For example, nucleosides comprising morpholino sugar moieties and their use in oligonucleotides have been reported. As used here, the term “morpholino” means a sugar surrogate having the following structure: OBx. morpholinos may be modified, for example, by adding or altering various substituent groups from the above morpholino structure. Such sugar surrogates are referred to herein as “modified morpholinos.” In certain embodiments, sugar surrogates comprise acyclic moieties. Examples of nucleosides and oligonucleotides comprising such acyclic sugar surrogates include, but are not limited to: peptide nucleic acid (“PNA”), acyclic butyl nucleic acid, and nucleosides and oligonucleotides described in Manoharan et al., U.S.10,913,767. Representative U.S. patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Patent Nos.5,539,082; 5,714,331; and 5,719,262. In certain embodiments, sugar surrogates are the “unlocked” sugar structure of UNA (unlocked nucleic acid) nucleosides. UNA is a nucleoside wherein any of the bonds of the sugar moiety has been removed, forming an unlocked sugar surrogate. A representative U.S. publication that teaches the preparation of UNA includes, but is not limited to, US Patent Publication No 2011 / 0313020. In certain embodiments, sugar surrogates are the glycerol as found in GNA (glycol nucleic acid) nucleosides as depicted below: (S)-GNA , any nucleobase. Many other bicyclic and tricyclic sugar and sugar surrogates are known in the art that can be used in modified nucleosides. 2. Certain Modified Nucleobases In certain embodiments, modified oligonucleotides comprise one or more nucleoside comprising an unmodified nucleobase. In certain embodiments, modified oligonucleotides comprise one or more nucleoside comprising a modified nucleobase. In certain embodiments, modified oligonucleotides comprise one or more nucleoside that does not comprise a nucleobase, referred to as an abasic nucleoside. In certain embodiments, modified oligonucleotides comprise one or more inosine nucleosides (i.e., nucleosides comprising a hypoxanthine nucleobase). An “unmodified nucleobase” is adenine (A), thymine (T), cytosine (C), uracil (U), or guanine (G). A modified nucleobase is a group of atoms other than unmodified A, T, C, U, or G capable of pairing with at least one other nucleobase. A 5-methylcytosine is an example of a modified nucleobase. A universal base is a modified nucleobase that can pair with any one of the five unmodified nucleobases. In certain embodiments, modified adenine has structure (I): substituted C1-C6alkyl, C1-C6thioalkyl, or substituted C1-C6thioalkyl, C1-C6alkyloxy, or substituted C1-C6alkyloxy; R6Ais H, N(Ra)(Rb), acetyl, formyl, or O-phenyl; Y7Ais N and R7Ais absent or is C1-C6alkyl; or Y7Ais C and R7Ais selected from H, C1-C6alkyl, or CN(Ra)(Rb); Y8Ais N and R8Ais absent, or Y8Ais C and R8Ais selected from H, a halogen, OH, C1-C6alkyl, or substituted C1-C6alkyl; Raand Rbare independently selected from H, C1-C6alkyl, substituted C1-C6alkyl, C1-C6alkenyl, substituted C1-C6alkenyl, acetyl, formyl, or together form a 5-7-membered heterocycle; excluding where Y7Ais N; Y8Ais C, R8Ais H, R2Ais H, and R6Ais NH2(unmodified adenine). In certain embodiments, modified guanine has structure (II): wherein: R2Gis N(Ra)(Rb); R6Gis oxo and R1Gis H, or R6Gis selected from O-C1-C6alkyl or S-C1-C6alkyl and R1Gis absent; Y7Gis N and R7Ais absent or is C1-C6alkyl; or Y7Gis C and R7Gis selected from H, C1- C6alkyl, or CN(Ra)(Rb); Y8Gis N and R8Gis absent, or Y8Gis C and R8Gis selected from H, a halogen, OH, C1- C6alkyl, or substituted C1-C6alkyl; Raand Rbare independently selected from H, C1-C6alkyl, substituted C1- C6alkyl, C1-C6alkenyl, substituted C1-C6alkenyl, acetyl, formyl, or together form a 5-7-membered heterocycle; excluding where Y7Gis N; Y8Gis C, R8Gis H, R2Gis NH2, and R6Gis =O (unmodified guanosine). In certain embodiments, modified thymine or modified uracil has structure (III): w ere n: X s se ected from O or S and R5Uis selected from H, OH, halogen, O-C1-C12alkyl, O-C1-C12substituted alkyl, C1-C12alkyl , substituted C1-C12alkyl, C1-C12alkenyl, substituted C1-C12alkenyl; wherein if each X is O, R5Uis not H or CH3(unmodified uracil and unmodified thymine, respectively). In certain embodiments, modified cytosine has structure (IV): wherein: X is selected from O or S, R4Cis N(Ra)(Rb); R5Cis selected from H, OH, halogen, O-C1-C12alkyl, O-C1-C12substituted alkyl, C1-C12alkyl , substituted C1-C12alkyl, C1-C12alkenyl, substituted C1-C12alkenyl; Raand Rbare independently selected from H, C1-C6alkyl, substituted C1-C6alkyl, C1-C6alkenyl, substituted C1-C6alkenyl, acetyl, formyl, or together form a 5-7-membered heterocycle; excluding where X is O, R4Cis NH2and R5Cis H (unmodified cytosine). In certain embodiments, modified nucleobases are selected from: 5-substituted pyrimidines, 6- azapyrimidines, alkyl or alkynyl substituted pyrimidines, alkyl substituted purines, and N-2, N-6 and O-6 substituted purines. In certain embodiments, modified nucleobases are selected from: 5-methylcytosine, 2- aminopropyladenine, 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-N- methylguanine, 6-N-methyladenine, 2-propyladenine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5- propynyl (-C^C-CH3) uracil, 5-propynylcytosine, 6-azouracil, 6-azocytosine, 6-azothymine, 5-ribosyluracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl, 8-aza and other 8-substituted purines, 5-halo (particularly 5-bromo), 5-trifluoromethyl, 5-halouracil, and 5-halocytosine, 7-methylguanine, 7-methyladenine, 2-F-adenine, 2-aminoadenine, 7-deazaguanine, 7-deazaadenine, 3-deazaguanine, 3- deazaadenine, 6-N-benzoyladenine, 2-N-isobutyrylguanine, 4-N-benzoylcytosine, 4-N-benzoyluracil, 5- methyl 4-N-benzoylcytosine, 5-methyl 4-N-benzoyluracil, universal bases, hydrophobic bases, promiscuous bases, size-expanded bases, and fluorinated bases. Further modified nucleobases include tricyclic pyrimidines, such as 1,3-diazaphenoxazine-2-one, 1,3-diazaphenothiazine-2-one and 9-(2-aminoethoxy)-1,3- diazaphenoxazine-2-one (G-clamp). Modified nucleobases may also include those in which the purine or pyrimidine base is replaced with other heterocycles, for example 7-deaza-adenine, 7-deazaguanosine, 2- aminopyridine and 2-pyridone. Further nucleobases include those disclosed in Englisch et al., Angewandte Chemie, International Edition, 1991, 30, 613; Sanghvi, Y.S., Chapter 15, Antisense Research and Applications, Crooke, S.T. and Lebleu, B., Eds., CRC Press, 1993, 273-288; and those disclosed in Chapters 6 and 15, Antisense Drug Technology, Crooke S.T., Ed., CRC Press, 2008, 163-166 and 442-443. Publications that teach the preparation of certain of the above noted modified nucleobases, as well as other modified nucleobases include without limitation, Rogers et al., U.S.5,134,066 ; Benner et al., U.S. 5,432,272; Matteucci et al., U.S.5,502,177 ; Froehler et al., U.S.5,594,121 ; and Cook et al., U.S.5,681,941. In certain embodiments, each nucleobase of a modified oligonucleotide of the invention is selected from A, G, C, T, U, andmC. In certain embodiments, each nucleobase of a modified oligonucleotide of the invention is selected from A, G, T, andmC (i.e., unmodified purines and 5-methyl pyrimidines). 3. Certain Modified Internucleoside Linkages The naturally occurring internucleoside linkage of RNA and DNA is a 3' to 5' phosphodiester linkage. In certain embodiments, nucleosides of modified oligonucleotides may be linked together using one or more modified internucleoside linkages. The two main classes of internucleoside linking groups are defined by the presence or absence of a phosphorus atom. Representative phosphorus-containing internucleoside linkages include, but are not limited to, phosphodiesters, which contain a phosphodiester bond (“P=O”) (also referred to as unmodified or naturally occurring linkages), phosphotriesters, methylphosphonates, phosphoramidates, phosphorothioates (“P=S”), and phosphorodithioates (“HS-P=S”). Representative non-phosphorus containing internucleoside linking groups include, but are not limited to, methylenemethylimino (-CH2-N(CH3)-O-CH2-), thiodiester, thionocarbamate (-O-C(=O)(NH)-S-); siloxane (- O-SiH2-O-); and N,N'-dimethylhydrazine (-CH2-N(CH3)-N(CH3)-). Modified internucleoside linkages, compared to naturally occurring phosphodiester internucleoside linkages, can be used to alter, typically increase, nuclease resistance of the oligonucleotide. In certain embodiments, internucleoside linkages having a chiral atom can be prepared as a racemic mixture, or as separate enantiomers. Methods of preparation of phosphorous-containing and non-phosphorous-containing internucleoside linkages are well known to those skilled in the art. In certain embodiments, a modified internucleoside linkage has Formula Z1, Z2, or Z3: wherein independently for each internucleoside linking group of Formula Z1, Z2, or Z3: each X1is independently selected from O and S; X2is selected from O, NR1, CH2, and S; X3is selected from O, NR1, CH2, and S; L is absent, NR1, N(R1)SO2, –N=, O, C1-C6alkylene, or C1-C6heteroalkylene; each R1is independently selected from H, C1-C6alkyl, and substituted C1-C6alkyl, or two R1on the same atom together form =O; and R2is selected from -OH, -SH, C1-C22alkyl, substituted C1-C22alkyl, C2-C22alkenyl, substituted C2- C22alkenyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, heteroaryl, substituted heteroaryl, aryl, and substituted aryl; wherein when a group is substituted, it comprises one or more substituent groups selected from halo, -OH, N(R1)2, -O-C1-C6alkyl, C1-C22alkyl, C2-C22alkenyl, cycloalkyl, heterocyclyl, heteroaryl, and aryl. In certain embodiments, a modified internucleoside linkage is any of those described in WO2021 / 030778, incorporated by reference herein. In certain embodiments, a modified internucleoside linkage comprises formula Z4: wherein independently for each such internucleoside linking group of a modified oligonucleotide: X is selected from O or S; R1is selected from H, C1-C6alkyl, and substituted C1-C6alkyl; and T is selected from SO2R2, C(=O)R3, and P(=O)R4R5, wherein: R2is selected from an aryl, a substituted aryl, a heterocycle, a substituted heterocycle, an aromatic heterocycle, a substituted aromatic heterocycle, a diazole, a substituted diazole, a C1-C6alkoxy, C1-C6alkyl, C1-C6alkenyl, C1-C6alkynyl, substituted C1-C6alkyl, substituted C1-C6alkenyl substituted C1-C6alkynyl, and a conjugate group; R3is selected from an aryl, a substituted aryl, CH3, N(CH3)2, OCH3and a conjugate group; R4is selected from OCH3, OH, C1-C6alkyl, substituted C1-C6alkyl and a conjugate group; and R5is selected from OCH3, OH, C1-C6alkyl, and substituted C1-C6alkyl. In certain embodiments, a modified internucleoside linkage comprises a mesyl phosphoramidate linking group which has the formula: . The mesyl linkage comprises a chiral center. In certain embodiments, modified oligonucleotides comprise (Rp) and / or (Sp) mesyl phosphoramidates, which are shown in the following formulas, respectively, wherein “B” indicates a nucleobase: . linkage may comprise a chiral center. In certain embodiments, modified oligonucleotides comprising (Rp) and / or (Sp) phosphorothioates comprise one or more of the following formulas, respectively, wherein “B” indicates a nucleobase: . Representative internucleoside linkages having a chiral center include but are not limited to alkylphosphonates and phosphorothioates. Modified oligonucleotides comprising internucleoside linkages having a chiral center can be prepared as populations of modified oligonucleotides comprising stereorandom internucleoside linkages, or as populations of modified oligonucleotides comprising such internucleoside linkages in particular stereochemical configurations. In certain embodiments, populations of modified oligonucleotides comprise phosphorothioate internucleoside linkages wherein all of the phosphorothioate internucleoside linkages are stereorandom. In certain embodiments, populations of modified oligonucleotides comprise mesyl phosphoramidate internucleoside linkages wherein all of the mesyl phosphoramidate internucleoside linkages are stereorandom. Such modified oligonucleotides can be generated using synthetic methods that result in random selection of the stereochemical configuration of each internucleoside linkage having a chiral center. Nonetheless, each individual internucleoside linkage having a chiral center of each individual oligonucleotide molecule has a defined stereoconfiguration. In certain embodiments, populations of modified oligonucleotides are enriched for modified oligonucleotides comprising one or more particular phosphorothioate and / or mesyl phosphoramidate internucleoside linkages, each independently in a particular, independently selected stereochemical configuration. In certain embodiments, the particular configuration of the particular phosphorothioate and / or mesyl phosphoramidate linkage is present in at least 65% of the molecules in the population. In certain embodiments, the particular configuration of the particular phosphorothioate and / or mesyl phosphoramidate linkage is present in at least 70% of the molecules in the population. In certain embodiments, the particular configuration of the particular phosphorothioate and / or mesyl phosphoramidate linkage is present in at least 80% of the molecules in the population. In certain embodiments, the particular configuration of the particular phosphorothioate and / or mesyl phosphoramidate linkage is present in at least 90% of the molecules in the population. In certain embodiments, the particular configuration of the particular phosphorothioate and / or mesyl phosphoramidate linkage is present in at least 99% of the molecules in the population. Such chirally enriched populations of modified oligonucleotides can be generated using synthetic methods known in the art, e.g., methods described in Oka et al., JACS 125, 8307 (2003), Wan et al. Nuc. Acid. Res.42, 13456 (2014), and WO 2017 / 015555. In certain embodiments, a population of modified oligonucleotides is enriched for modified oligonucleotides having at least one indicated phosphorothioate and / or mesyl phosphoramidate in the (Sp) configuration. In certain embodiments, a population of modified oligonucleotides is enriched for modified oligonucleotides having at least one phosphorothioate and / or mesyl phosphoramidate in the (Rp) configuration. Unless otherwise indicated, internucleoside linkages having chiral centers of modified oligonucleotides described herein can be stereorandom or in a particular stereochemical configuration. Neutral internucleoside linkages include, without limitation, phosphotriesters, methylphosphonates, MMI (3'-CH2-N(CH3)-O-5'), amide-3 (3'-CH2-C(=O)-N(H)-5'), amide-4 (3'-CH2-N(H)-C(=O)-5'), formacetal (3'-O-CH2-O-5'), methoxypropyl (MOP), and thioformacetal (3'-S-CH2-O-5'). Further neutral internucleoside linkages include nonionic linkages comprising siloxane (dialkylsiloxane), carboxylate ester, carboxamide, sulfide, sulfonate ester and amides (See for example: Carbohydrate Modifications in Antisense Research; Y.S. Sanghvi and P.D. Cook, Eds., ACS Symposium Series 580; Chapters 3 and 4, 40-65). Further neutral internucleoside linkages include nonionic linkages comprising mixed N, O, S and CH2component parts. In certain embodiments, modified oligonucleotides comprise one or more inverted nucleoside, as shown below: , any nucleobase. In certain embodiments, an inverted nucleoside is terminal (i.e., the last nucleoside on one end of an oligonucleotide) and so only one internucleoside linkage depicted above will be present. In certain such embodiments, additional features (such as a conjugate group) may be attached to the inverted nucleoside. Such terminal inverted nucleosides can be attached to either or both ends of an oligonucleotide.

[0002] In certain embodiments, nucleic acids can be linked 2’ to 5’ rather than the standard 3’ to 5’ linkage. Such a linkage is illustrated below. , any nucleobase. B. Certain Motifs In certain embodiments, modified oligonucleotides comprise one or more modified nucleosides comprising a modified sugar moiety. In certain embodiments, modified oligonucleotides comprise one or more modified nucleosides comprising a modified nucleobase. In certain embodiments, modified oligonucleotides comprise one or more modified internucleoside linkage. In such embodiments, the modified, unmodified, and differently modified sugar moieties, nucleobases, and / or internucleoside linkages of a modified oligonucleotide define a pattern or motif. In certain embodiments, the patterns of sugar moieties, nucleobases, and internucleoside linkages are each independent of one another. Thus, a modified oligonucleotide may be described by its sugar motif, nucleobase motif and / or internucleoside linkage motif (as used herein, nucleobase motif describes the modifications to the nucleobases independent of the sequence of nucleobases). 1. Certain Sugar Motifs In certain embodiments, oligonucleotides comprise one or more type of modified sugar and / or unmodified sugar moiety arranged along the oligonucleotide or region thereof in a defined pattern or sugar motif. In certain instances, such sugar motifs include but are not limited to any of the sugar modifications discussed herein. In certain embodiments, modified oligonucleotides comprise a deoxy region. In certain embodiments, each nucleoside of the deoxy region is a 2’-β-D-deoxynucleoside. In certain embodiments, the deoxy region consists of 5-12 linked nucleosides. In certain embodiments, the deoxy region consists of 6, 7, 8, 9, 10, or 6-10 linked nucleosides. In certain embodiments, at least one nucleoside within the deoxy region comprises a modified sugar moiety. In certain embodiments, exactly one nucleoside within the deoxy region comprises a modified sugar moiety. In certain embodiments, two or three nucleosides within the deoxy region comprise a modified sugar moiety. In certain embodiments, the deoxy region is flanked on the 5’-side by a 5’-region consisting of linked 5’-region nucleosides and on the 3’-side by a 3’-region consisting of linked 3’-region nucleosides; wherein the 3’-most nucleoside of the 5’-region is a modified nucleoside and the 5’-most nucleoside of the 3’-region is a modified nucleoside. At least one nucleoside of the 5’-region comprises a modified sugar moiety; and at least one nucleoside of the 3’-region comprises a modified sugar moiety. The three regions (the 5’-region, the deoxy region, and the 3’-region) form a contiguous sequence of nucleosides. In certain embodiments, the sugar moiety of the 3’-most nucleoside of the 5’-region and the sugar moiety of the 5’-most nucleoside of the 3’-region each differ from the sugar moiety of the respective adjacent nucleoside of the deoxy region, thus defining the boundary between the 5’-region, the deoxy region, and the 3’-region. In certain embodiments, each nucleoside of the 5’-region and each nucleoside of the 3’-region comprises a modified sugar moiety. In certain embodiments, the nucleosides within the 5’-region comprise the same sugar modification. In certain embodiments, the nucleosides within the 5’-region comprise two or more different sugar modifications. In certain embodiments, the nucleosides within the 3’-region comprise the same sugar modification. In certain embodiments, the nucleosides within the 3’-region comprise two or more different sugar modifications. In certain embodiments, the 5’-region and the 3’-region of a modified oligonucleotide each comprises 1-8 nucleosides. In certain embodiments, the 5’-region comprises 1-7 nucleosides. In certain embodiments, the 5’-region comprises 1-6 nucleosides. In certain embodiments, the 5’-region comprises 1, 2, 3, 4, 5, 6, 7, or 8 nucleosides. In certain embodiments, the 3’-region comprises 1-7 nucleosides. In certain embodiments, the 3’-region comprises 1-6 nucleosides. In certain embodiments, the 3’-region comprises 1, 2, 3, 4, 5, 6, 7, or 8 nucleosides. In certain embodiments, modified oligonucleotides comprise or consist of a region having a gapmer motif, which is defined by two external regions or “wings” and a central or internal region or “gap.” The three regions of a gapmer motif (the 5’-wing, the gap, and the 3’-wing) form a contiguous sequence of nucleosides wherein at least some of the sugar moieties of the nucleosides of each of the wings differ from at least some of the sugar moieties of the nucleosides of the gap. Specifically, at least the sugar moieties of the nucleosides of each wing that are closest to the gap (the 3’-most nucleoside of the 5’-wing and the 5’-most nucleoside of the 3’-wing) differ from the sugar moiety of the neighboring gap nucleosides, thus defining the boundary between the wings and the gap (i.e., the wing / gap junction). In certain embodiments, the sugar moieties within the gap are the same as one another. In certain embodiments, the gap includes one or more nucleoside having a sugar moiety that differs from the sugar moiety of one or more other nucleosides of the gap. In certain embodiments, the sugar motifs of the two wings are the same as one another (symmetric gapmer). In certain embodiments, the sugar motif of the 5'-wing differs from the sugar motif of the 3'-wing (asymmetric gapmer). In certain embodiments, the wings of a gapmer comprise 1-6 nucleosides. In certain embodiments, each nucleoside of each wing of a gapmer comprises a modified sugar moiety. In certain embodiments, at least one nucleoside of each wing of a gapmer comprises a modified sugar moiety. In certain embodiments, at least two nucleosides of each wing of a gapmer comprises a modified sugar moiety. In certain embodiments, at least three nucleosides of each wing of a gapmer comprises a modified sugar moiety. In certain embodiments, at least four nucleosides of each wing of a gapmer comprises a modified sugar moiety. In certain embodiments, at least five nucleosides of each wing of a gapmer comprises a modified sugar moiety. In certain embodiments, the gap of a gapmer comprises 7-12 nucleosides. In certain embodiments, each nucleoside of the gap of a gapmer comprises a 2’-β-D-deoxyribosyl sugar moiety. In certain embodiments, at least one nucleoside of the gap of a gapmer comprises a modified sugar moiety. In certain embodiments, the gapmer is a deoxy gapmer. In certain embodiments, the nucleosides on the gap side of each wing / gap junction comprise 2’-β-D-deoxyribosyl sugar moieties and the nucleosides on the wing sides of each wing / gap junction comprise modified sugar moieties. In certain embodiments, each nucleoside of the gap comprises a 2’-β-D-deoxyribosyl sugar moiety. In certain embodiments, each nucleoside of each wing of a gapmer comprises a modified sugar moiety. In certain embodiments, at least one nucleoside of the gap of a gapmer comprises a modified sugar moiety. In certain embodiments, at least one nucleoside of the gap of a gapmer comprises a 2’-OMe sugar moiety. In certain embodiments, modified oligonucleotides comprise or consist of a portion having a fully modified sugar motif. In such embodiments, each nucleoside of the fully modified portion of the modified oligonucleotide comprises a modified sugar moiety. In certain embodiments, each nucleoside of the entire modified oligonucleotide comprises a modified sugar moiety. In certain embodiments, modified oligonucleotides comprise or consist of a portion having a fully modified sugar motif, wherein each nucleoside within the fully modified portion comprises the same modified sugar moiety, referred to herein as a uniformly modified sugar motif. In certain embodiments, a fully modified oligonucleotide is a uniformly modified oligonucleotide. In certain embodiments, each nucleoside of a uniformly modified oligonucleotide comprises the same 2’-modification. In certain embodiments, the modified oligonucleotide comprises a block of 16, 17, 18, 19, or 20 contiguous 2’-MOE sugar moieties. In certain embodiments, the modified oligonucleotide comprises a uniform MOE motif, in which each sugar moiety of the modified oligonucleotide comprises a 2’-MOE sugar moiety. In certain embodiments, the modified oligonucleotide comprises a block of 16, 17, 18, 19, or 20 contiguous 2’-NMA sugar moieties. In certain embodiments, the modified oligonucleotide comprises a uniform NMA motif, in which each sugar moiety of the modified oligonucleotide comprises a 2’-NMA sugar moiety. Herein, the lengths (number of nucleosides) of the three regions of a gapmer may be provided using the notation [# of nucleosides in the 5’-wing] – [# of nucleosides in the gap] – [# of nucleosides in the 3’- wing]. Thus, a 3-10-3 gapmer consists of 3 linked nucleosides in each wing and 10 linked nucleosides in the gap. Where such nomenclature is followed by a specific modification, that modification is the modification in each sugar moiety of each wing and the gap nucleosides comprise 2’-β-D-deoxyribosyl sugar moieties. Thus, a 5-10-5 MOE gapmer consists of 5 linked 2’-MOE nucleosides in the 5’-wing, 10 linked 2’- β-D- deoxynucleosides in the gap, and 5 linked 2’-MOE nucleosides in the 3’-wing. A 3-10-3 cEt gapmer consists of 3 linked cEt nucleosides in the 5’-wing, 10 linked 2’- β-D-deoxynucleosides in the gap, and 3 linked cEt nucleosides in the 3’-wing. A 5-8-5 gapmer consists of 5 linked nucleosides comprising a modified sugar moiety in the 5’-wing, 8 linked 2’-β-D-deoxynucleosides in the gap, and 5 linked nucleosides comprising a modified sugar moiety in the 3’-wing. A 5-8-5 mixed gapmer has at least two different modified sugar moieties in the 5’- and / or the 3’-wing, two different modified sugar moieties in the gap region, or a combination thereof. In certain embodiments, modified oligonucleotides disclosed herein are modified by a specific sugar modification. In certain embodiments, modified oligonucleotides are 5-10-5 MOE gapmers. In certain embodiments, modified oligonucleotides are 3-10-3 BNA gapmers. In certain embodiments, modified oligonucleotides are 3-10-3 cEt gapmers. In certain embodiments, modified oligonucleotides are 3-10-3 LNA gapmers. In certain embodiments, modified oligonucleotides are 3-10-4 cEt gapmers. In certain embodiments, modified oligonucleotides are 4-10-3 cEt gapmers. In certain embodiments, modified oligonucleotides are 4-10-4 cEt gapmers. In certain embodiments, 5-10-5 cEt gapmers. In certain embodiments, modified oligonucleotides are 6-10-4 MOE gapmers. In certain embodiments, modified oligonucleotides disclosed herein are modified by two or more sugar modifications. In certain embodiments, modified oligonucleotides are 3-10-3 mixed gapmers, wherein each nucleoside within the 5’ and the 3’ wings comprises a modified sugar moiety selected from a 2’-MOE sugar moiety and a 2’-cEt sugar moiety, and the gap nucleosides comprise 2’-β-D-deoxyribosyl sugar moieties. In certain embodiments, modified oligonucleotides are 3-10-4 mixed gapmers, wherein each nucleoside within the 5’ and the 3’ wings comprises a modified sugar moiety selected from a 2’-MOE sugar moiety and a 2’-cEt sugar moiety, and the gap nucleosides comprise 2’-β-D-deoxyribosyl sugar moieties. In certain embodiments, modified oligonucleotides are 3-10-5 mixed gapmers, wherein each nucleoside within the 5’ and the 3’ wings comprises a modified sugar moiety selected from a 2’-MOE sugar moiety and a 2’- cEt sugar moiety, and the gap nucleosides comprise 2’-β-D-deoxyribosyl sugar moieties. In certain embodiments, modified oligonucleotides are 4-9-4 mixed gapmers, wherein each nucleoside within the 5’ and the 3’ wings comprises a modified sugar moiety selected from a 2’-MOE sugar moiety and a 2’-cEt sugar moiety, and the gap nucleosides comprise 2’-β-D-deoxyribosyl sugar moieties. In certain embodiments, modified oligonucleotides are 5-10-5 mixed gapmers, wherein each nucleoside within the 5’ and the 3’ wings comprises a modified sugar moiety selected from a 2’-MOE sugar moiety and a 2’-cEt sugar moiety, and the gap nucleosides comprise 2’-β-D-deoxyribosyl sugar moieties. In certain embodiments, modified oligonucleotides are 6-10-4 mixed gapmers, wherein each nucleoside within the 5’ and the 3’ wings comprises a modified sugar moiety selected from a 2’-MOE sugar moiety and a 2’-cEt sugar moiety, and the gap nucleosides comprise 2’-β-D-deoxyribosyl sugar moieties. In certain embodiments, modified oligonucleotides disclosed herein are modified by two or more sugar modifications within the gap region. In certain embodiments, modified oligonucleotides are 3-10-3 mixed gapmers, wherein each nucleoside within the 5’ and the 3’ wings comprises a 2’-cEt sugar moiety, and each nucleoside within the gap comprises a sugar moiety selected from a 2’-OMe sugar moiety or a 2’-β-D- deoxyribosyl sugar moiety. In certain embodiments, modified oligonucleotides are 5-10-5 mixed gapmers, wherein each nucleoside within the 5’ and the 3’ wings comprises a 2’-MOE sugar moiety, and each nucleoside within the gap comprises a sugar moiety selected from a 2’-β-D-deoxyxylosyl sugar moiety, a 2’- α-L-deoxyribosyl sugar moiety, and 2’-β-D-deoxyribosyl sugar moiety. In certain embodiments, modified oligonucleotides have a sugar motif of 5’- eeeeeddddddddddeeeee -3’, wherein each “e” represents a 2’-MOE sugar moiety, and each “d” represents a 2’-β-D-deoxyribosyl sugar moiety. In certain embodiments, modified oligonucleotides have a sugar motif of 5’- eeeeeeddddddddddeeee -3’, wherein each “e” represents a 2’-MOE sugar moiety, and each “d” represents a 2’-β-D-deoxyribosyl sugar moiety. 2. Certain Nucleobase Motifs In certain embodiments, oligonucleotides comprise modified and / or unmodified nucleobases arranged along the oligonucleotide or region thereof in a defined pattern or motif. In certain embodiments, each nucleobase is modified. In certain embodiments, none of the nucleobases are modified. In certain embodiments, each purine or each pyrimidine is modified. In certain embodiments, each adenine is modified. In certain embodiments, each guanine is modified. In certain embodiments, each thymine is modified. In certain embodiments, each uracil is modified. In certain embodiments, each cytosine is modified. In certain embodiments, some or all of the cytosine nucleobases in a modified oligonucleotide are 5-methylcytosines. In certain embodiments, all of the cytosine nucleobases are 5-methylcytosines and all of the other nucleobases of the modified oligonucleotide are unmodified nucleobases. In certain embodiments, modified oligonucleotides comprise a block of modified nucleobases. In certain such embodiments, the block is at the 3’-end of the oligonucleotide. In certain embodiments, the block is within 3 nucleosides of the 3’-end of the oligonucleotide. In certain embodiments, the block is at the 5’-end of the oligonucleotide. In certain embodiments, the block is within 3 nucleosides of the 5’-end of the oligonucleotide. In certain embodiments, oligonucleotides having a gapmer motif comprise a nucleoside comprising a modified nucleobase. In certain such embodiments, one nucleoside comprising a modified nucleobase is in the central gap of an oligonucleotide having a gapmer motif. In certain such embodiments, the sugar moiety of said nucleoside is a 2’- β-D-deoxyribosyl sugar moiety. In certain embodiments, the modified nucleobase is selected from a 2-thiopyrimidine and a 5-propynylpyrimidine. 3. Certain Internucleoside Linkage Motifs In certain embodiments, oligonucleotides comprise modified and / or unmodified internucleoside linkages arranged along the oligonucleotide or region thereof in a defined pattern or motif. In certain embodiments, each internucleoside linking group is a phosphodiester internucleoside linkage. In certain embodiments, each internucleoside linking group of a modified oligonucleotide is a phosphorothioate internucleoside linkage. In certain embodiments, each internucleoside linkage of a modified oligonucleotide is independently selected from a phosphorothioate internucleoside linkage and phosphodiester internucleoside linkage. In certain embodiments, each phosphorothioate internucleoside linkage is independently selected from a stereorandom phosphorothioate a (Sp) phosphorothioate, and a (Rp) phosphorothioate. In certain embodiments, the sugar motif of a modified oligonucleotide is a gapmer and the internucleoside linkages within the gap are all modified. In certain embodiments, some or all of the internucleoside linkages in the wings are unmodified phosphodiester internucleoside linkages. In certain embodiments, the terminal internucleoside linkages are modified. In certain embodiments, the sugar motif of a modified oligonucleotide is a gapmer, and the internucleoside linkage motif comprises at least one phosphodiester internucleoside linkage in at least one wing, wherein the at least one phosphodiester linkage is not a terminal internucleoside linkage, and the remaining internucleoside linkages are phosphorothioate internucleoside linkages. In certain such embodiments, all of the phosphorothioate linkages are stereorandom. In certain embodiments, all of the phosphorothioate linkages in the wings are (Sp) phosphorothioates, and the gap comprises at least one Sp, Sp, or Rp motif. In certain embodiments, populations of modified oligonucleotides are enriched for modified oligonucleotides comprising such internucleoside linkage motifs. In certain embodiments, modified oligonucleotides have an internucleoside linkage motif comprising one or more mesyl phosphoramidate linking groups. In certain embodiments, one or more phosphorothioate internucleoside linkages or one or more phosphodiester internucleoside linkages of the internucleoside linkage motifs herein is substituted with a mesyl phosphoramidate linking group. In certain embodiments, modified oligonucleotides have an internucleoside linkage motif of 5’- soooossssssssssooss -3’, wherein each “s” represents a phosphorothioate internucleoside linkage, and each “o” represents a phosphodiester internucleoside linkage. C. Certain Lengths It is possible to increase or decrease the length of an oligonucleotide without eliminating activity. For example, in Woolf et al. (Proc. Natl. Acad. Sci. USA 89:7305-7309, 1992), a series of oligonucleotides 13-25 nucleobases in length were tested for their ability to induce cleavage of a target RNA in an oocyte injection model. Oligonucleotides 25 nucleobases in length with 8 or 11 mismatch bases near the ends of the oligonucleotides were able to direct specific cleavage of the target RNA, albeit to a lesser extent than the oligonucleotides that contained no mismatches. Similarly, target specific cleavage was achieved using 13 nucleobase oligonucleotides, including those with 1 or 3 mismatches. In certain embodiments, oligonucleotides (including modified oligonucleotides) can have any of a variety of ranges of lengths. In certain embodiments, oligonucleotides consist of X to Y linked nucleosides, where X represents the fewest number of nucleosides in the range and Y represents the largest number nucleosides in the range. In certain such embodiments, X and Y are each independently selected from 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, and 50; provided that X≤Y. For example, in certain embodiments, oligonucleotides consist of 12 to 13, 12 to 14, 12 to 15, 12 to 16, 12 to 17, 12 to 18, 12 to 19, 12 to 20, 12 to 21, 12 to 22, 12 to 23, 12 to 24, 12 to 25, 12 to 26, 12 to 27, 12 to 28, 12 to 29, 12 to 30, 13 to 14, 13 to 15, 13 to 16, 13 to 17, 13 to 18, 13 to 19, 13 to 20, 13 to 21, 13 to 22, 13 to 23, 13 to 24, 13 to 25, 13 to 26, 13 to 27, 13 to 28, 13 to 29, 13 to 30, 14 to 15, 14 to 16, 14 to 17, 14 to 18, 14 to 19, 14 to 20, 14 to 21, 14 to 22, 14 to 23, 14 to 24, 14 to 25, 14 to 26, 14 to 27, 14 to 28, 14 to 29, 14 to 30, 15 to 16, 15 to 17, 15 to 18, 15 to 19, 15 to 20, 15 to 21, 15 to 22, 15 to 23, 15 to 24, 15 to 25, 15 to 26, 15 to 27, 15 to 28, 15 to 29, 15 to 30, 16 to 17, 16 to 18, 16 to 19, 16 to 20, 16 to 21, 16 to 22, 16 to 23, 16 to 24, 16 to 25, 16 to 26, 16 to 27, 16 to 28, 16 to 29, 16 to 30, 17 to 18, 17 to 19, 17 to 20, 17 to 21, 17 to 22, 17 to 23, 17 to 24, 17 to 25, 17 to 26, 17 to 27, 17 to 28, 17 to 29, 17 to 30, 18 to 19, 18 to 20, 18 to 21, 18 to 22, 18 to 23, 18 to 24, 18 to 25, 18 to 26, 18 to 27, 18 to 28, 18 to 29, 18 to 30, 19 to 20, 19 to 21, 19 to 22, 19 to 23, 19 to 24, 19 to 25, 19 to 26, 19 to 27, 19 to 28, 19 to 29, 19 to 30, 20 to 21, 20 to 22, 20 to 23, 20 to 24, 20 to 25, 20 to 26, 20 to 27, 20 to 28, 20 to 29, 20 to 30, 21 to 22, 21 to 23, 21 to 24, 21 to 25, 21 to 26, 21 to 27, 21 to 28, 21 to 29, 21 to 30, 22 to 23, 22 to 24, 22 to 25, 22 to 26, 22 to 27, 22 to 28, 22 to 29, 22 to 30, 23 to 24, 23 to 25, 23 to 26, 23 to 27, 23 to 28, 23 to 29, 23 to 30, 24 to 25, 24 to 26, 24 to 27, 24 to 28, 24 to 29, 24 to 30, 25 to 26, 25 to 27, 25 to 28, 25 to 29, 25 to 30, 26 to 27, 26 to 28, 26 to 29, 26 to 30, 27 to 28, 27 to 29, 27 to 30, 28 to 29, 28 to 30, or 29 to 30 linked nucleosides. In certain embodiments, oligonucleotides (including modified oligonucleotides) consist of 16 linked nucleosides. In certain embodiments, oligonucleotides (including modified oligonucleotides) consist of 17 linked nucleosides. In certain embodiments, oligonucleotides (including modified oligonucleotides) consist of 18 linked nucleosides. In certain embodiments, oligonucleotides (including modified oligonucleotides) consist of 19 linked nucleosides. In certain embodiments, oligonucleotides (including modified oligonucleotides) consist of 20 linked nucleosides. D. Certain Modified Oligonucleotides In certain embodiments, the above modifications (sugar, nucleobase, internucleoside linkage) are incorporated into a modified oligonucleotide. In certain embodiments, modified oligonucleotides are characterized by their modification motifs and overall lengths. In certain embodiments, such parameters are each independent of one another. Thus, unless otherwise indicated, each internucleoside linkage of an oligonucleotide having a gapmer sugar motif may be modified or unmodified and may or may not follow the gapmer modification pattern of the sugar modifications. For example, the internucleoside linkages within the wing regions of a sugar gapmer may be the same or different from one another and may be the same or different from the internucleoside linkages of the gap region of the sugar motif. Likewise, such sugar gapmer oligonucleotides may comprise one or more modified nucleobase independent of the gapmer pattern of the sugar modifications. Unless otherwise indicated, all modifications are independent of nucleobase sequence. E. Certain RNAi Modified Oligonucleotides Provided herein is an antisense RNAi oligonucleotide. Also provided is an RNAi agent comprising such an antisense RNAi oligonucleotide. An RNAi agent of the disclosure may be an oligomeric duplex comprising an antisense RNAi oligomeric compound comprising an antisense RNAi oligonucleotide and a sense RNAi oligomeric compound comprising a sense RNAi oligonucleotide. Both the antisense RNAi oligonucleotide and the sense RNAi oligonucleotide are characterized by respective motifs of sugar moieties which can be conceptually separated from the nucleobase sequences thereof. The motif or sequence of sugar moieties is known to affect loading into protein complexes which are relevant to knockdown of a target mRNA or pre-mRNA. See, e.g., Hu, B., et al. Therapeutic siRNA: state of the art. Sig Transduct Target Ther 5, 101 (2020). In certain embodiments, at least one nucleoside of a modified oligonucleotide comprises a 2’-OMe sugar moiety. In certain embodiments, at least 2, at least 5, at least 8, at least 10, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 nucleosides comprise a 2’-OMe sugar moiety. In certain embodiments, a modified oligonucleotide comprises one, two, or three blocks of at least 4 contiguous 2’-OMe nucleosides. In certain embodiments, an antisense RNAi oligonucleotide comprises 2’-OMe nucleosides at nucleosides 3-5, counting from the 5’-terminal nucleoside. In certain embodiments, an antisense RNAi oligonucleotide comprises 2’-OMe nucleosides at nucleosides 7- 11. In certain embodiments, an antisense RNAi oligonucleotide comprises 2’-OMe nucleosides at nucleosides 15 and 17-19. In certain embodiments, an antisense RNAi oligonucleotide comprises 2’-OMe nucleosides at nucleosides 3-13. In certain such embodiments the remainder of the nucleosides in the modified oligonucleotide are selected from 2’-deoxynucleosides, 2’-F nucleosides, 2’-MOE nucleosides, and 2’-OMe nucleosides. In certain embodiments, at least one nucleoside of a modified oligonucleotide comprises a 2’-F sugar moiety (i.e., a 2’-F modified nucleoside). In certain embodiments, a modified oligonucleotide comprises exactly 1, 2, 3, 4, or 5 nucleosides comprising a 2’-F sugar moiety. In certain embodiments, a modified oligonucleotide comprises a block of 2, 3, or 2-4 contiguous 2’-F nucleosides. In certain embodiments, an antisense RNAi oligonucleotide comprises a 2’-F nucleoside at one, two, three, or four of nucleosides 2, 6, 14, and / or 16, counting from the 5’-terminal nucleoside. In certain embodiments, an antisense RNAi oligonucleotide comprises a 2’-F nucleoside at one, two, or three of nucleosides 2, 14, and / or 16. In certain embodiments, an antisense RNAi oligonucleotide comprises a 2’-F nucleoside at one or two of nucleosides 2 and / or 14. In certain such embodiments, the remainder of the nucleosides in the modified oligonucleotide are selected from 2’-deoxy nucleosides, 2’-MOE nucleosides, and 2’-OMe nucleosides. In certain such embodiments, the remainder of the nucleosides in the modified oligonucleotide are 2’-OMe nucleosides. In any of the embodiments described herein, a modified oligonucleotide may comprise a nucleoside comprising an F-HNA sugar surrogate. In any of the embodiments described herein comprising a 2’-F nucleoside, one, two, three, one or more, or all such 2’-F nucleoside may be replaced with a nucleoside comprising an F-HNA sugar surrogate. In certain embodiments, the modified oligonucleotide comprises 1, 2, or 32’-deoxy sugar moieties. In certain embodiments, each 2’-deoxynucleoside of a modified oligonucleotide comprises a 2’-β-D- deoxyribosyl sugar moiety. In certain embodiments, all but one 2’-deoxynucleoside nucleoside of a modified oligonucleotide comprises a 2’-β-D-deoxyribosyl sugar moiety. In certain embodiments, an antisense RNAi oligonucleotide comprises a 2’-deoxy nucleoside at one or two of nucleosides 5, 6, and 7, counting from the 5’-terminal nucleoside. In certain embodiments, an antisense RNAi oligonucleotide comprises a 2’-deoxy nucleoside at nucleoside 6. In certain embodiments, an antisense RNAi oligonucleotide comprises a 2’-deoxy nucleoside at nucleosides 5 and 7. In certain such embodiments, the remainder of the nucleosides in the modified oligonucleotide are selected from 2’-F nucleosides, 2’-MOE nucleosides, and 2’-OMe nucleosides. In certain embodiments, the modified oligonucleotide comprises 1, 2, 3, 4 or 52’-MOE sugar moieties. In certain embodiments, an antisense RNAi oligonucleotide comprises a 2’-MOE nucleoside at one, two, three, four, or five of nucleosides 1, 9, 10, 22, and 23, counting from the 5’-terminal nucleoside. In certain embodiments, an antisense RNAi oligonucleotide comprises a 2’-MOE nucleoside at nucleoside 1. In certain embodiments, an antisense RNAi oligonucleotide comprises a 2’-MOE nucleoside at one or two of nucleosides 9 and / or 10. In certain embodiments, an antisense RNAi oligonucleotide comprises a 2’-MOE nucleoside at one or two of nucleosides 22 and / or 23. In certain such embodiments the remainder of the nucleosides in the modified oligonucleotide are selected from 2’-deoxy nucleosides, 2’-F nucleosides, and 2’- OMe nucleosides. Certain RNAi motifs are described in, e.g., Freier, et al., WO2020 / 160163, incorporated by reference herein in its entirety; as well as, e.g., Rajeev, et al., WO2013 / 075035; Maier, et al., WO2016 / 028649; Theile, et al., WO2018 / 098328; Nair, et al., WO2019 / 217459; each of which is incorporated by reference herein. In certain embodiments, a sugar motif of the antisense RNAi oligonucleotide is selected from those described in WO 2022 / 174053. In certain embodiments, a sugar motif of the sense RNAi oligonucleotide is selected from those described in WO 2022 / 174053. In certain embodiments, a modified oligonucleotide is a uniformly modified oligonucleotide in which each modified nucleoside comprises the same 2’-modification. In certain embodiments, every second nucleoside of a uniformly modified nucleotide comprises the same 2’-modification, providing alternating 2’- modifications. In certain such embodiments, the 2’ modifications are 2’-OMe and 2’-F (i.e., alternating 2’- OMe and 2’-F nucleosides). In certain embodiments, an RNAi agent described herein comprises two or more oligomeric duplexes. In certain embodiments, each oligomeric duplex comprises an antisense RNAi oligomeric compound comprising an antisense RNAi oligonucleotide and a sense RNAi oligomeric compound comprising a sense RNAi oligonucleotide. In certain embodiments, the two or more oligomeric duplexes are linked together. In certain embodiments, the two or more oligomeric duplexes are covalently linked together. In certain embodiments, the sense RNAi oligomeric compound of the two or more oligomeric duplexes are covalently linked together. In certain embodiments, the sense RNAi oligomeric compounds are covalently linked together at their 3’ end. In certain embodiments, the two or more oligomeric duplexes are covalently linked together by a glycol linker, such as a tetraethylene glycol linker. In certain embodiments, the RNAi agent comprises an siRNA architecture described in, e.g., Alterman, et al., Nature Biotech., 2019, 37:844- 894. F. Nucleobase Sequence In certain embodiments, oligonucleotides (or portions thereof) have a nucleobase sequence that is complementary to a second oligonucleotide or an identified reference nucleic acid (or portion thereof), such as a target nucleic acid. In certain embodiments, the nucleobase sequence of a region or entire length of an oligonucleotide is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% complementary to the second oligonucleotide or identified reference nucleic acid (or portion thereof), such as a target nucleic acid. VI. Certain Oligomeric Compounds In certain embodiments, provided herein are oligomeric compounds, which comprises an oligonucleotide and optionally one or more conjugate groups and / or terminal groups. A conjugate group consists of a conjugate moiety and a conjugate linker which links the conjugate moiety to the oligonucleotide. Conjugate groups may be attached to either or both ends of an oligonucleotide and / or at any internal position. In certain embodiments, conjugate groups are attached to the 2'-position of a nucleoside of a modified oligonucleotide. In certain embodiments, conjugate groups are attached to either or both ends of an oligonucleotide (such conjugate groups are also terminal groups). In certain such embodiments, conjugate groups or terminal groups are attached at the 3’ and / or 5’-end of oligonucleotides. A. Certain Conjugate Groups In certain embodiments, oligonucleotides are covalently attached to one or more conjugate groups. In certain embodiments, conjugate groups modify one or more properties of the attached oligonucleotide, including but not limited to pharmacodynamics, pharmacokinetics, stability, binding, absorption, tissue distribution, cellular distribution, cellular uptake, charge and clearance. In certain embodiments, conjugation of one or more carbohydrate moieties to a modified oligonucleotide can alter one or more properties of the modified oligonucleotide. In certain embodiments, the carbohydrate moiety is attached to a modified subunit of the modified oligonucleotide. For example, the ribose sugar of one or more ribonucleotide subunits of a modified oligonucleotide can be replaced with another moiety, e.g. a non-carbohydrate (preferably cyclic) carrier to which is attached a carbohydrate ligand. A ribonucleotide subunit in which the ribose sugar of the subunit has been so replaced is referred to herein as a ribose replacement modification subunit (RRMS), which is a modified sugar moiety. A cyclic carrier may be a carbocyclic ring system, i.e., one or more ring atoms may be a heteroatom, e.g., nitrogen, oxygen, sulphur. The cyclic carrier may be a monocyclic ring system, or may contain two or more rings, e.g. fused rings. The cyclic carrier may be a fully saturated ring system, or it may contain one or more double bonds. In certain embodiments, the modified oligonucleotide is a gapmer. In certain embodiments, conjugate groups impart a new property on the attached oligonucleotide, e.g., fluorophores or reporter groups that enable detection of the oligonucleotide. Certain conjugate groups and conjugate moieties have been described previously, for example: cholesterol moiety (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989, 86, 6553-6556), cholic acid (Manoharan et al., Bioorg. Med. Chem. Lett., 1994, 4, 1053-1060), a thioether, e.g., hexyl-S-tritylthiol (Manoharan et al., Ann. N.Y. Acad. Sci., 1992, 660, 306-309; Manoharan et al., Bioorg. Med. Chem. Lett., 1993, 3, 2765-2770), a thiocholesterol (Oberhauser et al., Nucl. Acids Res., 1992, 20, 533-538), an aliphatic chain, e.g., do-decan-diol or undecyl residues (Saison- Behmoaras et al., EMBO J., 1991, 10, 1111-1118; Kabanov et al., FEBS Lett., 1990, 259, 327-330; Svinarchuk et al., Biochimie, 1993, 75, 49-54), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethyl-ammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654; Shea et al., Nucl. Acids Res., 1990, 18, 3777-3783), a polyamine or a polyethylene glycol chain (Manoharan et al., Nucleosides & Nucleotides, 1995, 14, 969-973), or adamantane acetic acid a palmityl moiety (Mishra et al., Biochim. Biophys. Acta, 1995, 1264, 229-237), an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277, 923-937), a tocopherol group (Nishina et al., Molecular Therapy Nucleic Acids, 2015, 4, e220; and Nishina et al., Molecular Therapy, 2008, 16, 734-740), or a GalNAc cluster (e.g., WO2014 / 179620). In certain embodiments, a conjugate group consists of a lipid and a conjugate linker. In certain embodiments, a conjugate group is a phosphate linked lipid having the following structure: . Conjugate moieties include, without limitation, intercalators, reporter molecules, polyamines, polyamides, peptides, carbohydrates (e.g., GalNAc), antibodies, vitamin moieties, polyethylene glycols, thioethers, polyethers, cholesterols, thiocholesterols, cholic acid moieties, folate, lipids, phospholipids, biotin, phenazine, phenanthridine, anthraquinone, adamantane, acridine, fluoresceins, rhodamines, coumarins, fluorophores, and dyes. In certain embodiments, a conjugate moiety comprises an active drug substance, for example, aspirin, warfarin, phenylbutazone, ibuprofen, suprofen, fen-bufen, ketoprofen, (S)-(+)-pranoprofen, carprofen, dansylsarcosine, 2,3,5-triiodobenzoic acid, fingolimod, flufenamic acid, folinic acid, a benzothiadiazide, chlorothiazide, a diazepine, indo-methicin, a barbiturate, a cephalosporin, a sulfa drug, an antidiabetic, an antibacterial or an antibiotic. In certain embodiments, conjugate moieties are selected from any of C22 alkyl, C20 alkyl, C21 alkyl, C19 alkyl, C18 alkyl, C17 alkyl, C16 alkyl, C15 alkyl, C14 alkyl, C13 alkyl, C12 alkyl, C11 alkyl, C10 alkyl, C9 alkyl, C8 alkyl, C7 alkyl, C6 alkyl, C5 alkyl, C22 alkenyl, C20 alkenyl, C21 alkenyl, C19 alkenyl, C18 alkenyl, C17 alkenyl, C16 alkenyl, C15 alkenyl, C14 alkenyl, C13 alkenyl, C12 alkenyl, C11 alkenyl, C10 alkenyl, C9 alkenyl, C8 alkenyl, C7 alkenyl, C6 alkenyl, or C5 alkenyl. In certain embodiments, conjugate moieties are selected from any of C22 alkyl, C20 alkyl, C21 alkyl, C19 alkyl, C18 alkyl, C17 alkyl, C16 alkyl, C15 alkyl, C14 alkyl, C13 alkyl, C12 alkyl, C11 alkyl, C10 alkyl, C9 alkyl, C8 alkyl, C7 alkyl, C6 alkyl, or C5 alkyl, where the alkyl chain has one or more unsaturated bonds. In certain embodiments, the conjugate moiety is a C16 linear alkyl group. In certain embodiments, the conjugate moiety is a C16 linear alkyl group attached at the 2’-position of a sugar moiety of a modified nucleoside. 2. Conjugate Linkers Conjugate moieties are attached to oligonucleotides through conjugate linkers. In certain oligomeric compounds, the conjugate linker is a single chemical bond (i.e., the conjugate moiety is attached directly to an oligonucleotide through a single bond). In certain embodiments, the conjugate linker comprises a chain structure, such as a hydrocarbyl chain, or an oligomer of repeating units such as ethylene glycol, nucleosides, or amino acid units. In certain embodiments, a conjugate linker comprises pyrrolidine. In certain embodiments, a conjugate linker comprises one or more groups selected from alkyl, amino, oxo, amide, disulfide, polyethylene glycol, ether, thioether, and hydroxylamino. In certain such embodiments, the conjugate linker comprises groups selected from alkyl, amino, oxo, amide and ether groups. In certain embodiments, the conjugate linker comprises groups selected from alkyl and amide groups. In certain embodiments, the conjugate linker comprises groups selected from alkyl and ether groups. In certain embodiments, the conjugate linker comprises at least one phosphorus moiety. In certain embodiments, the conjugate linker comprises at least one phosphate group. In certain embodiments, the conjugate linker includes at least one neutral linking group. In certain embodiments, conjugate linkers, including the conjugate linkers described above, are bifunctional linking moieties, e.g., those known in the art to be useful for attaching conjugate groups to compounds, such as the oligonucleotides provided herein. In general, a bifunctional linking moiety comprises at least two functional groups. One of the functional groups is selected to bind to a particular site on a compound and the other is selected to bind to a conjugate group. Examples of functional groups used in a bifunctional linking moiety include but are not limited to electrophiles for reacting with nucleophilic groups and nucleophiles for reacting with electrophilic groups. In certain embodiments, bifunctional linking moieties comprise one or more groups selected from amino, hydroxyl, carboxylic acid, thiol, alkyl, alkenyl, and alkynyl. Examples of conjugate linkers include but are not limited to pyrrolidine, 8-amino-3,6-dioxaoctanoic acid (ADO), succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) and 6-aminohexanoic acid (AHEX or AHA). Other conjugate linkers include but are not limited to substituted or unsubstituted C1- C10alkyl, substituted or unsubstituted C2-C10alkenyl or substituted or unsubstituted C2-C10alkynyl, wherein a nonlimiting list of preferred substituent groups includes hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl. In certain embodiments, conjugate linkers comprise 1-10 linker-nucleosides. In certain embodiments, conjugate linkers comprise 2-5 linker-nucleosides. In certain embodiments, conjugate linkers comprise exactly 3 linker-nucleosides. In certain embodiments, conjugate linkers comprise the TCA motif. In certain embodiments, such linker-nucleosides are modified nucleosides. In certain embodiments such linker- nucleosides comprise a modified sugar moiety. In certain embodiments, linker-nucleosides are unmodified. In certain embodiments, linker-nucleosides comprise an optionally protected heterocyclic base selected from a purine, substituted purine, pyrimidine or substituted pyrimidine. In certain embodiments, a cleavable moiety is a nucleoside selected from uracil, thymine, cytosine, 4-N-benzoylcytosine, 5-methylcytosine, 4-N-benzoyl- 5-methylcytosine, adenine, 6-N-benzoyladenine, guanine and 2-N-isobutyrylguanine. It is typically desirable for linker-nucleosides to be cleaved from the oligomeric compound after it reaches a target tissue. Accordingly, linker-nucleosides are typically linked to one another and to the remainder of the oligomeric compound through cleavable bonds. In certain embodiments, such cleavable bonds are phosphodiester bonds. Herein, linker-nucleosides are not considered to be part of the oligonucleotide. Accordingly, in embodiments in which an oligomeric compound comprises an oligonucleotide consisting of a specified number or range of linked nucleosides and / or a specified percent complementarity to a reference nucleic acid and the oligomeric compound also comprises a conjugate group comprising a conjugate linker comprising linker-nucleosides, those linker-nucleosides are not counted toward the length of the oligonucleotide and are not used in determining the percent complementarity of the oligonucleotide for the reference nucleic acid. For example, an oligomeric compound may comprise (1) a modified oligonucleotide consisting of 8-30 nucleosides and (2) a conjugate group comprising 1-10 linker-nucleosides that are contiguous with the nucleosides of the modified oligonucleotide. The total number of contiguous linked nucleosides in such an oligomeric compound is more than 30. Alternatively, an oligomeric compound may comprise a modified oligonucleotide consisting of 8-30 nucleosides and no conjugate group. The total number of contiguous linked nucleosides in such an oligomeric compound is no more than 30. Unless otherwise indicated conjugate linkers comprise no more than 10 linker-nucleosides. In certain embodiments, conjugate linkers comprise no more than 5 linker-nucleosides. In certain embodiments, conjugate linkers comprise no more than 3 linker- nucleosides. In certain embodiments, conjugate linkers comprise no more than 2 linker-nucleosides. In certain embodiments, conjugate linkers comprise no more than 1 linker-nucleoside. In certain embodiments, it is desirable for a conjugate group to be cleaved from the oligonucleotide. For example, in certain circumstances oligomeric compounds comprising a particular conjugate moiety are better taken up by a particular cell type, but once the oligomeric compound has been taken up, it is desirable that the conjugate group be cleaved to release the unconjugated or parent oligonucleotide. Thus, certain conjugate linkers may comprise one or more cleavable moieties. In certain embodiments, a cleavable moiety is a cleavable bond. In certain embodiments, a cleavable moiety is a group of atoms comprising at least one cleavable bond. In certain embodiments, a cleavable moiety comprises a group of atoms having one, two, three, four, or more than four cleavable bonds. In certain embodiments, a cleavable moiety is selectively cleaved inside a cell or subcellular compartment, such as a lysosome. In certain embodiments, a cleavable moiety is selectively cleaved by endogenous enzymes, such as nucleases. In certain embodiments, a cleavable bond is selected from: an amide, an ester, an ether, one or both esters of a phosphodiester, a phosphate ester, a carbamate, or a disulfide. In certain embodiments, a cleavable bond is one or both of the esters of a phosphodiester. In certain embodiments, a cleavable moiety comprises a phosphate or phosphodiester. In certain embodiments, the cleavable moiety is a phosphate linkage between an oligonucleotide and a conjugate moiety or conjugate group. In certain embodiments, a cleavable moiety comprises or consists of one or more linker-nucleosides. In certain such embodiments, the one or more linker-nucleosides are linked to one another and / or to the remainder of the oligomeric compound through cleavable bonds. In certain embodiments, such cleavable bonds are unmodified phosphodiester bonds. In certain embodiments, a cleavable moiety is 2'- deoxynucleoside that is attached to either the 3' or 5'-terminal nucleoside of an oligonucleotide by a phosphate internucleoside linkage and covalently attached to the remainder of the conjugate linker or conjugate moiety by a phosphate or phosphorothioate linkage. In certain such embodiments, the cleavable moiety is 2'-deoxyadenosine. 3. Cell-Targeting Moieties In certain embodiments, a conjugate group comprises a cell-targeting moiety. In certain embodiments, the cell-targeting moiety targets neurons. In certain embodiments, the cell-targeting moiety targets a neurotransmitter receptor. In certain embodiments, the cell targeting moiety targets a neurotransmitter transporter. In certain embodiments, the cell targeting moiety targets a GABA transporter. See e.g., WO 2011 / 131693, WO 2014 / 064257. In certain embodiments, conjugate groups comprise cell-targeting moieties that have affinities for transferrin receptor (TfR) (also referred to herein as TfR1 and CD71). In certain embodiments, a conjugate group described herein comprises an anti-TfR1 antibody or fragment thereof. In certain embodiments, the conjugate group comprises a protein or peptide capable of binding TfR1. In certain embodiments, the conjugate group comprises an aptamer capable of binding TfR1. In certain embodiments, the anti-TfR1 antibody or fragment thereof can be any known in the art including but not limited to those described in WO1991 / 004753; WO2013 / 103800; WO2014 / 144060; WO2016 / 081643; WO2016 / 179257; WO2016 / 207240; WO2017 / 221883; WO2018 / 129384; WO2018 / 124121; WO2019 / 151539; WO2020 / 132584; WO2020 / 028864; US 7,208,174; US 9,034,329; US 10,550,188; and US 11,512,136. In certain embodiments, a fragment of an anti-TfR1 antibody is a F(ab′)2, Fab, Fab′, Fv, scFv, VHH, or VNAR. In certain embodiments, an antibody binds to TfR1 through an engineered Fc domain rather than through the antigen-binding portion, as described in, e.g., US 2020 / 0223935. In certain embodiments, the conjugate group comprises a protein or peptide capable of binding TfR1 that does not include the antigen-binding fragment of an antibody. In certain embodiments, the protein or peptide capable of binding TfR1 may be any known in the art including but not limited to those described in WO 2019 / 140050; WO 2020 / 037150; WO 2020 / 124032; WO 2022 / 026555; WO 2023 / 027125; WO 2023 / 022234; and US 10,138,483. In certain embodiments, the peptide is a cyclic peptide, as described in WO 2021 / 167107. In certain embodiments, the peptide is a bicyclic peptide known as a ‘bicycle ligand’ selected from those described in WO 2022 / 101633 and WO 2023 / 056388. In certain embodiments, the conjugate group comprises an aptamer capable of binding TfR1. In certain embodiments, the aptamer capable of binding TfR1 can be any known in the art including but not limited to those described in WO2013 / 163303; WO2019 / 033051; and WO2020 / 245198. B. Certain Terminal Groups In certain embodiments, oligomeric compounds comprise one or more terminal groups. In certain such embodiments, oligomeric compounds comprise a stabilized 5’-phosphate. Stabilized 5’-phosphates include, but are not limited to 5’-phosphonates, including, but not limited to 5’-vinylphosphonates. In certain embodiments, terminal groups comprise one or more abasic sugar moieties and / or inverted nucleosides. In certain embodiments, an terminal group comprises an inverted abasic sugar moiety. In certain embodiments, the inverted abasic sugar moiety may be further attached to a conjugate group. In certain embodiments, terminal groups comprise one or more 2’-linked nucleosides or sugar moieties. In certain such embodiments, the 2’-linked group is an abasic sugar moiety. Such terminal abasic sugar moieties can be attached to either or both ends of an oligonucleotide. In any of the oligomeric duplexes described herein, the first oligomeric compound can comprise a stabilized phosphate group at the 5’ position of the 5’-most nucleoside. In any of the oligomeric duplexes described herein, the first oligomeric compound can comprise a stabilized phosphate group attached to the 5’ position of the 5’-most nucleoside. In certain embodiments, an antisense RNAi oligonucleotide comprises a stabilized phosphate group at the 5’-most nucleoside. In certain embodiments, the stabilized phosphate group comprises a cyclopropyl phosphonate or an (E)-vinyl phosphonate. In certain embodiments, the stabilized phosphate group is an (E)-vinyl phosphonate. Certain stabilized phosphates are described in WO2010 / 048585, WO2010 / 048549, WO 2011 / 139702, WO 2017 / 214112, WO 2018 / 045317, and WO 2024 / 062413. In certain embodiments, the stabilized phosphate group has a structure , moiety, optionally to the 4’-position of a furanosyl sugar moiety, and wherein Re1and Re2are independently selected from hydrogen, halo (for example, fluoro), OH, O-C1-6alkyl, NH2, NHC1-6alkyl, N(C1-6alkyl)2, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, and C2-6alkynyl, and wherein Ring E is a 3-4 membered cycloalkyl ring optionally substituted with 1-4 groups independently selected from halo (for example, fluoro), OH, O-C1-6alkyl, NH2, NHC1-6alkyl, N(C1-6alkyl)2, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, and C2-6alkynyl. VII. Antisense Activity In certain embodiments, oligomeric compounds are capable of hybridizing to a target nucleic acid, resulting in at least one antisense activity. In certain embodiments, antisense compounds are deemed to have antisense activity when they reduce or inhibit the amount or activity of a target nucleic acid by 50% or more in the standard in vitro assay. In certain embodiments, antisense compounds selectively affect one or more target nucleic acid. Such antisense compounds comprise a nucleobase sequence that hybridizes to one or more target nucleic acid, resulting in one or more desired antisense activity and does not hybridize to one or more non-target nucleic acid or does not hybridize to one or more non-target nucleic acid in such a way that results in significant undesired antisense activity. In certain antisense activities, hybridization of an antisense compound to a target nucleic acid results in recruitment of a protein that cleaves the target nucleic acid. For example, certain antisense compounds result in RNase H mediated cleavage of the target nucleic acid. RNase H is a cellular endonuclease that cleaves the RNA strand of an RNA:DNA duplex. The DNA in such an RNA:DNA duplex need not be unmodified DNA. In certain embodiments, described herein are antisense compounds that are sufficiently “DNA-like” to elicit RNase H activity. In certain embodiments, one or more non-DNA-like nucleoside in the gap of a gapmer is tolerated. In certain antisense activities, an antisense compound or a portion of an antisense compound is loaded into an RNA-induced silencing complex (RISC), ultimately resulting in cleavage of the target nucleic acid. For example, certain antisense compounds result in cleavage of the target nucleic acid by Argonaute. Antisense compounds that are loaded into RISC are RNAi agents. RNAi agents may be double-stranded (siRNA or dsRNAi) or single-stranded (ssRNAi). In certain embodiments, hybridization of an antisense compound to a target nucleic acid does not result in recruitment of a protein that cleaves that target nucleic acid. In certain embodiments, hybridization of the antisense compound to the target nucleic acid results in alteration of splicing of the target nucleic acid. In certain embodiments, hybridization of an antisense compound to a target nucleic acid results in inhibition of a binding interaction between the target nucleic acid and a protein or other nucleic acid. In certain embodiments, hybridization of an antisense compound to a target nucleic acid results in alteration of translation of the target nucleic acid. Antisense activities may be observed directly or indirectly. In certain embodiments, observation or detection of an antisense activity involves observation or detection of a change in an amount of a target nucleic acid or protein encoded by such target nucleic acid, a change in the ratio of splice variants of a nucleic acid or protein and / or a phenotypic change in a cell or subject. VIII. Certain Target Nucleic Acids In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to a target nucleic acid. In certain embodiments, the target nucleic acid is an endogenous RNA molecule. In certain embodiments, the target nucleic acid encodes a protein. In certain such embodiments, the target nucleic acid is selected from: a mature mRNA and a pre-mRNA, including intronic, exonic and untranslated regions. In certain embodiments, the target RNA is a mature mRNA. In certain embodiments, the target nucleic acid is a pre-mRNA. In certain embodiments, the target region is entirely within an intron. In certain embodiments, the target region spans an intron / exon junction. In certain embodiments, the target region is at least 50% within an intron. In certain embodiments, the target nucleic acid is the RNA transcriptional product of a retrogene. In certain embodiments, the target nucleic acid is a non-coding RNA. In certain embodiments, the target non-coding RNA is selected from: a long non-coding RNA, a short non-coding RNA, an intronic RNA molecule. A. Complementarity / Mismatches to the Target Nucleic Acid In certain embodiments, oligonucleotides are complementary to the target nucleic acid over the entire length of the oligonucleotide. In certain embodiments, oligonucleotides are 80%, 85%, 90%, 95%, or 99% complementary to the target nucleic acid. In certain embodiments, oligonucleotides are at least 80% complementary to the target nucleic acid over the entire length of the oligonucleotide and comprise a region that is 100% or fully complementary to a target nucleic acid. In certain embodiments, the region of full complementarity is from 6 to 20, 10 to 18, or 18 to 20 nucleobases in length. It is possible to introduce mismatch bases without eliminating activity. For example, Gautschi et al (J. Natl. Cancer Inst.93:463-471, March 2001) demonstrated the ability of an oligonucleotide having 100% complementarity to the bcl-2 mRNA and having 3 mismatches to the bcl-xL mRNA to reduce the expression of both bcl-2 and bcl-xL in vitro and in vivo. Furthermore, this oligonucleotide demonstrated potent anti- tumor activity in vivo. Maher and Dolnick (Nuc. Acid. Res.16:3341-3358, 1988) tested a series of tandem 14 nucleobase oligonucleotides, and 28 and 42 nucleobase oligonucleotides comprised of the sequence of two or three of the tandem oligonucleotides, respectively, for their ability to arrest translation of human DHFR in a rabbit reticulocyte assay. Each of the three 14 nucleobase oligonucleotides alone was able to inhibit translation, albeit at a more modest level than the 28 or 42 nucleobase oligonucleotides. In certain embodiments, oligonucleotides comprise one or more mismatched nucleobases relative to the target nucleic acid. In certain embodiments, antisense activity against the target is reduced by such mismatch, but activity against a non-target is reduced by a greater amount. Thus, in certain embodiments selectivity of the oligonucleotide is improved. In certain embodiments, a mismatch is specifically positioned within an oligonucleotide having a gapmer motif. In certain embodiments, the mismatch is at position 1, 2, 3, 4, 5, 6, 7, or 8 from the 5’-end of the gap region. In certain embodiments, the mismatch is at position 9, 8, 7, 6, 5, 4, 3, 2, 1 from the 3’-end of the gap region (with position 1 at the 3’-end of the gap region). In certain embodiments, the mismatch is at position 1, 2, 3, or 4 from the 5’-end of the 5’ wing region. In certain embodiments, the mismatch is at position 4, 3, 2, or 1 from the 3’-end of the 5’ wing region (with position 1 at the 3’-end of the 5’ wing region). In certain embodiments, the mismatch is at position 1, 2, 3, or 4 from the 5’-end of the 3’ wing region. In certain embodiments, the mismatch is at position 4, 3, 2, or 1 from the 3’-end of the 3’ wing region (with position 1 at the 3’ terminus of the oligonucleotide). B. Certain Targets In certain embodiments, oligomeric compounds comprise or consist of an oligonucleotide comprising a region that is complementary to a target nucleic acid, wherein the target nucleic acid is APOE, APP, ATXN1, ATXN2, ATXN3, C9ORF72, GFAP, GYS1, HTT, KCNT1, LRRK2, PLP1, PMP22, PRNP, SCN1A, SMN2, SNCA, STMN2, or UBE3A-ATS. In certain embodiments, the oligonucleotide is a modified oligonucleotide. In certain embodiments, the oligomeric compound comprises an antisense RNase H oligonucleotide. In certain embodiments, the oligomeric compound comprises an antisense RNAi oligonucleotide. In certain embodiments, the oligomeric compound comprises a splice-modulating oligonucleotide. In certain embodiments, the oligomeric compound comprises a steric-blocking oligonucleotide. In some embodiments, the oligomeric compound comprises a conjugate group. In other embodiments, the oligomeric compound does not comprise a conjugate group. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to APOE. In certain embodiments, the APOE nucleic acid has the sequence set forth in SEQ ID NO: 1 (GENBANK Accession No. NC_000019.10, truncated from nucleotides 44903001 to 44912000), SEQ ID NO: 2 (GENBANK Accession No. NM_001302688.1), SEQ ID NO: 3 (GENBANK Accession No. AU126799.1), SEQ ID NO: 4 (GENBANK Accession No. BI602495. l), SEQ ID NO: 5 (the complement of GENBANK Accession No. CA306379.1), or SEQ ID NO: 6 (GENBANK Accession No. NM_000041.2 with T-->C at pos 471 to result in APOE4 mutant mRNA). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of APOE, e.g., of SEQ ID NOs: 1-6. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of APOE, e.g., of SEQ ID NOs: 1-6. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to APP. In certain embodiments, the APP nucleic acid has the sequence set forth in SEQ ID NO: 7 (the cDNA of Ensembl transcript ENST00000346798.7 from version 94: October 2018), the complement of SEQ ID NO: 8 (GENBANK Accession No. NC_000021.9 truncated from nucleotides 25878001 to 26174000), SEQ ID NO: 9 (the cDNA of Ensembl transcript ENST00000357903.7 from version 94: October 2018), SEQ ID NO: 10 (the cDNA of Ensembl transcript ENST00000348990.9 from version 94: October 2018), SEQ ID NO: 11 (the cDNA of Ensembl transcript ENST00000440126.7 from version 94: October 2018), SEQ ID NO: 12 (the cDNA of Ensembl transcript ENST00000354192.7 from version 94: October 2018), SEQ ID NO: 13 (the cDNA of Ensembl transcript ENST00000358918.7 from version 94: October 2018), or SEQ ID NO: 14 (GENBANK Accession No. NM_201414.2). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of APP, e.g., of SEQ ID NOs: 7-14. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of APP, e.g., of SEQ ID NOs: 7-14. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to ATXN1. In certain embodiments, the ATXN1 nucleic acid has the sequence set forth in SEQ ID NO: 15 (GENBANK Accession No. NM_000332.3), SEQ ID NO: 16 (the complement of GENBANK Accession No. NC_000006.12 truncated from nucleotides 1629600l to 16764000), SEQ ID NO: 17 (GENBANK Accession No. NM_001128164.l), SEQ ID NO: 18 (GENBANK Accession No. BC011026.1), SEQ ID NO: 19 (GENBANK Accession No. BC029401.1), or SEQ ID NO: 20 (GENBANK Accession No. BC047894.1). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of ATXN1, e.g., of SEQ ID NOs: 15-20. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of ATXN1, e.g., of SEQ ID NOs: 15-20. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to ATXN2. In certain embodiments, the ATXN2 nucleic acid has the sequence set forth in SEQ ID NO: 21 (GENBANK Accession No: NM_002973.3) or SEQ ID NO: 22 (the complement of GENBANK Accession No: NT_009775.17 truncated from nucleotides 2465000 to 2616000). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of ATXN2, e.g., of SEQ ID NOs: 21-22. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of ATXN2, e.g., of SEQ ID NOs: 21-22. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to ATXN3. In certain embodiments, the ATXN3 nucleic acid has the sequence set forth in SEQ ID NO: 23 (GENBANK Accession No: NM_004993.5); SEQ ID NO: 24 (the complement of GENBANK Accession No NC_000014.9 truncated from nucleotides 92,056,001 to 92,110,000); SEQ ID NO: 25 (GENBANK Accession No: NM_001164781.1); SEQ ID NO: 26 (GENBANK Accession No: NM_001127697.2); or SEQ ID NO: 27 (Ensembl transcript No: ENST00000558190.5). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of ATXN3, e.g., of SEQ ID NOs: 23-27. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of ATXN3, e.g., of SEQ ID NOs: 23-27. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to C9ORF72. In certain embodiments, the C9ORF72 nucleic acid has the sequence set forth in SEQ ID NO: 28 (the complement of GENBANK Accession No. NM_001256054.1), SEQ ID NO: 29 (the complement of GENBANK Accession No. NT_008413.18 truncated from nucleobase 27535000 to 27565000), SEQ ID NO: 30 (GENBANK Accession No. BQ068108.1), SEQ ID NO: 31 (GENBANK Accession No. NM_018325.3), SEQ ID NO: 32 (GENBANK Accession No. DN993522.1), SEQ ID NO: 33 (GENBANK Accession No. NM_145005.5), SEQ ID NO: 34 (GENBANK Accession No. DB079375.1), or SEQ ID NO: 35 (GENBANK Accession No. BU194591.1). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of C9ORF72, e.g., of SEQ ID NOs: 28-35. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of C9ORF72, e.g., of SEQ ID NOs: 28-35. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to GFAP. In certain embodiments, the GFAP nucleic acid has the sequence set forth in SEQ ID NO: 36 (GENBANK Accession No. NM_002055.4), SEQ ID NO: 37 (GENBANK Accession No. NC_000017.11 truncated from nucleotides 44903001 to 44919000), or SEQ ID NO: 38 (GENBANK Accession No. NM_001131019.2). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of GFAP, e.g., of SEQ ID NOs: 36-38. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of GFAP, e.g., of SEQ ID NOs: 36-38. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to GYS1. In certain embodiments, the GYS1 nucleic acid has the sequence set forth in SEQ ID NO: 39 (GENBANK Accession No. NM_002103.4), SEQ ID NO: 40 (the complement of GENBANK Accession No. NC_000019.10 truncated from nucleotides 48965001 to 48996000), SEQ ID NO: 41 (HG19 CHR19:49468258-49499257(-)), SEQ ID NO: 42 (GENBANK Accession No. NG_012923.1), SEQ ID NO: 43 (UCSC ID: UC002PLP.3), SEQ ID NO: 44 (UCSC ID: UC010EMM.3), SEQ ID NO: 45 (UCSC ID: UC010XZZ.2), SEQ ID NO: 46 (GENBANK Accession No. NM_001161587.1), SEQ ID NO: 47 (GENBANK Accession No. NR_027763.1), SEQ ID NO: 48 (GENBANK Accession No. AK303712.1), or SEQ ID NO: 49 (ENSEMBL GENE ID: ENSG00000104812.15 from Ensembl Release 108 (Oct 2022)). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of GYS1, e.g., of SEQ ID NOs: 39-49. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of GYS1, e.g., of SEQ ID NOs: 39-49. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to HTT. In certain embodiments, the HTT nucleic acid has the sequence set forth in SEQ ID NO: 50 (GENBANK Accession No. NM_002111.6) or SEQ ID NO: 51 (GENBANK Accession No. NT_006081.17 truncated from nucleotides 462000 to 634000). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of HTT, e.g., of SEQ ID NOs: 50- 51. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of HTT, e.g., of SEQ ID NOs: 50-51. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to KCNT1. In certain embodiments, the KCNT1 nucleic acid has the sequence set forth in SEQ ID NO: 52 (GENBANK Accession No: NM_020822.2), SEQ ID NO: 53 (GENBANK Accession No: NC_000009.12 truncated from nucleotides 135698001 to 135796000), or SEQ ID NO: 54 (GENBANK Accession No.: NM_020822.3), which is a splicing variant of SEQ ID NO: 52. In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of KCNT1, e.g., of SEQ ID NOs: 52-54. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of KCNT1, e.g., of SEQ ID NOs: 52-54. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to LRRK2. In certain embodiments, the LRRK2 nucleic acid has the sequence set forth in SEQ ID NO: 55 (GENBANK Accession No: NM_198578.3) or SEQ ID NO: 56 (GENBANK Accession No: NT_029419.11 truncated from nucleotides 2759000 to 2909000). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of LRRK2, e.g., of SEQ ID NOs: 55-56. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of LRRK2, e.g., of SEQ ID NOs: 55-56. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to PLP1. In certain embodiments, the PLP1 nucleic acid has the sequence set forth in SEQ ID NO: 57 (GENBANK Accession No. NM_001128834.2) or SEQ ID NO: 58 (GENBANK Accession No. NC_000023.11 truncated from nucleotides 103773001 to 103795000). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of PLP1, e.g., of SEQ ID NOs: 57-58. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of PLP1, e.g., of SEQ ID NOs: 57-58. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to PMP22. In certain embodiments, the PMP22 nucleic acid has the sequence set forth in SEQ ID NO: 59 (GENBANK Accession No. NM_000304.3), SEQ ID NO: 60 (GENBANK Accession No. NC_000017.11 truncated from nucleotides 15227001 to 15268000), SEQ ID NO: 61 (GENBANK Accession No. NM_153321.2), SEQ ID NO: 62 (GENBANK Accession No. NM_001281455.1), SEQ ID NO: 63 (GENBANK Accession No. NM_001281456.1), SEQ ID NO: 64 (GENBANK Accession No. NR_104017.1), SEQ ID NO:65 (GENBANK Accession No. NR_104018.1), or SEQ ID NO: 66 (GENBANK Accession No. AK300690.1). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of PMP22, e.g., of SEQ ID NOs: 59-66. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of PMP22, e.g., of SEQ ID NOs: 59-66. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to PRNP. In certain embodiments, the PRNP nucleic acid has the sequence set forth in SEQ ID NO: 67 (GENBANK Accession No: NM_000311.4), SEQ ID NO: 68 (GENBANK Accession No: NC_000020.11 truncated from nucleotides 4683001 to 4705000), SEQ ID NO: 69 (GENBANK Accession No.: NM_001080123.2), which is a splicing variant of SEQ ID NO: 67, or SEQ ID NO: 70 (ENSEMBL Accession No. ENST00000359125.6 from ENSEMBL version 98: September 2019, human reference assembly version GRCh38.pl3 located on the reverse strand of chromosome 20 (CM000682.2) from positions 63,406,137 to 63,472,590; Yates, et al., "Ensembl 2020", Nucleic Acids Research, gkz966, 2019), which is a splicing variant of SEQ ID NO: 1. In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of PRNP, e.g., of SEQ ID NOs: 67-70. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of PRNP, e.g., of SEQ ID NOs: 67-70. In certain embodiments, oligomeric compounds comprise or consist of a modified oligonucleotide that is complementary to a target nucleic acid encoding SCN1A, or a portion thereof. In certain embodiments, the SCN1A target nucleic acid has the nucleobase sequence set forth in SEQ ID NO: 97 (the complement of GENBANK Accession No. NC_000002.12 truncated from nucleotides 165982001 to 166152000). In certain embodiments, the SCN1A target nucleic acid has the nucleobase sequence set forth in SEQ ID NO: 98 (GENBANK Accession No. NM_001165963.2). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of SCN1A, e.g., of SEQ ID NO: 97 or 98. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of SCN1A, e.g., of SEQ ID NO: 97 or 98. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to SMN2. In certain embodiments, the SMN2 nucleic acid has the sequence set forth in SEQ ID NO: 71 (GENBANK Accession No. NT_006713.14 truncated from nucleotides 19939708 to 19967777). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of SMN2, e.g., of SEQ ID NO: 71. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of SMN2, e.g., of SEQ ID NO: 71. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to SNCA. In certain embodiments, the SNCA nucleic acid has the sequence set forth in SEQ ID NO: 72 (Ensembl Accession ENSG00000145335.17, Ensembl release 106 - Apr 2022), SEQ ID NO: 73 (the complement of GENBANK Accession No: NT_016354.20 truncated from nucleoside 30800000 to nucleoside 30919000), SEQ ID NO: 74 (GENBANK Accession No: NM_001146055.1), SEQ ID NO: 75 (Ensembl ID ENST00000618500.4, Ensembl release 106-Apr 2022), SEQ ID NO: 76 (GENBANK Accession No: NM_000345.3), SEQ ID NO: 77 (GENBANK Accession No: JN709863.1), SEQ ID NO: 78 (GENBANK Accession No: BC013293.2), SEQ ID NO: 79 (GENBANK Accession No: NM_001146054.2), or SEQ ID NO: 80 (GENBANK Accession No: HQ830269.l). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of SNCA, e.g., of SEQ ID NOs: 72-80. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of SNCA, e.g., of SEQ ID NOs: 72-80. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to STMN2. In certain embodiments, the STMN2 nucleic acid has the sequence set forth in SEQ ID NO: 81 (complement of GENBANK Accession No. NC 000008.11 truncated from nucleobase 79608001 to 79669000). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of STMN2, e.g., of SEQ ID NO: 81. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of STMN2, e.g., of SEQ ID NO: 81. In certain embodiments, oligomeric compounds described herein comprise or consists of an oligonucleotide comprising a region that is complementary to UBE3A-ATS. In certain embodiments, the UBE3A-ATS nucleic acid has the sequence set forth in SEQ ID NO: 82 (GENBANK Accession No: NC_000015.10_TRUNC_24821647_25441028), SEQ ID NO: 83 (Ensembl Gene ID ENSG00000224078), or SEQ ID NO: 84 (the cDNA of Ensembl transcript ENST00000554726.1). In certain embodiments, the nucleobase sequence of the oligonucleotide (e.g., a modified oligonucleotide) is at least 80%, 85%, 90%, 95%, or 100% complementary to an equal length portion of UBE3A-ATS, e.g., of SEQ ID NOs: 82-84. In certain embodiments, the oligonucleotide (e.g., a modified oligonucleotide) has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases complementary to an equal length portion of UBE3A-ATS, e.g., of SEQ ID NOs: 82-84. C. Certain Tissues In certain embodiments, the pharmaceutical composition comprises an oligomeric compound comprising a modified oligonucleotide, and a pharmaceutically acceptable diluent. In certain embodiments, the modified oligonucleotide comprises a region that is complementary to a target nucleic acid. In certain embodiments, the target nucleic acid is APOE, APP, ATXN1, ATXN2, ATXN3, C9ORF72, GFAP, GYS1, HTT, KCNT1, LRRK2, PLP1, PMP22, PRNP, SCN1A, SMN2, SNCA, STMN2, or UBE3A-ATS. In certain embodiments, the target nucleic acid is expressed in a cell of the central nervous system (CNS), In certain embodiments, the cell is a brain cell, or is from the spinal cord. In certain embodiments, the cell is a neuron. In certain embodiments, the cell is a glial cell. In certain embodiments, the cell is an oligodendrocyte, an astrocyte, a microglia, or an ependymal cell, or its respective progenitor cell. D. Certain Methods In certain embodiments, provided is a method comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition as provided herein. In certain embodiments, the subject is a primate. In certain embodiments, provided is a pharmaceutical composition comprising a modified oligonucleotide, wherein the oligonucleotide is complementary to a target nucleic acid, wherein the target nucleic acid is expressed in a cell of the central nervous system (CNS), for example, where the target nucleic acid is as described herein. In certain embodiments, the target nucleic acid is expressed in a brain cell, such as a neuron, glial cell, an oligodendrocyte, an astrocyte, a microglia, or an ependymal cell, or its respective progenitor cell. In certain embodiments, provided is a method comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition as provided herein, wherein the subject has a neurodegenerative disease or a neurodevelopmental disorder, for example dementia, a channelopathy, a tauopathy, a synucleinopathy, a spinocerebellar ataxia, for example Alexander disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Angelman Syndrome, Charcot-Marie-Tooth disease, epilepsy, Friedreich ataxia, frontotemporal dementia, Huntington’s disease, Lafora disease, Lewy body disease, Parkinson’s disease, Pelizaeus-Merzbacher disease, prion disease, or spinal muscular atrophy. In certain embodiments, the subject experiences reduced, for example, no, acute neurotoxicity compared to administration of an analogous pharmaceutical composition not including excess divalent cation, for example aCSF. In certain embodiments, the acute neurotoxicity is an acute activation. In certain embodiments, an acute activation score is determined based on level of phenotypes, wherein the levels of phenotypes are (scores indicated in parenthesis): (1) tremors, twitch, salivation, self-biting, or urinary incontinence; (2) combination of two of the level 1 symptoms, or nystagmus; (3) tonic, or clonic convulsion; (4) tonic-clonic convulsion; (5) seizure; (6) severe multiple seizures; (7) euthanasia required for humane reasons, wherein subject receives the highest observed level if a phenotype is observed. In certain embodiments, the subject is observed for the first hour after administration and again 3-4 hours later. In certain embodiments, the acute activation following administration of the analogous pharmaceutical composition not including excess divalent cation, for example aCSF, lasts no more than 120 minutes, no more than 90 minutes, no more than 60 minutes, no more than 50 minutes, no more than 45 minutes, no more than 40 minutes, no more than 35 minutes, no more than 30 minutes, no more than 25 minutes, no more than 20 minutes, no more than 15 minutes, no more than 10 minutes, or no more than 5 minutes in the subject post administration. In certain embodiments, a symptom of an acute activation improves or is resolved in 120 minutes, 90 minutes, 60 minutes, 50 minutes, 45 minutes, 40 minutes, 35 minutes, 30 minutes, 25 minutes, 20 minutes, 15 minutes, or 10 minutes post symptom onset, wherein the symptom is, for example, muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, nystagmus, urinary incontinence, increased muscle cramping or spasms, convulsions, or seizures. In certain embodiments, administration of the pharmaceutical composition does not induce an acute sedation in the subject. In certain embodiments, the pharmaceutical composition is administered by intrathecal or intracerebroventricular administration. In certain embodiments, the subject is a human. IX. Exemplary Oligomeric Compounds In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide comprising a region that targets a target nucleic acid. In certain embodiments, the target nucleic acid is APOE, APP, ATXN1, ATXN2, ATXN3, C9ORF72, GFAP, GYS1, HTT, KCNT1, LRRK2, PLP1, PMP22, PRNP, SCN1A, SMN2, SNCA, STMN2, or UBE3A-ATS. In certain embodiments, the modified oligonucleotide consists of 12 to 50 linked nucleosides. In certain embodiments, the modified oligonucleotide consists of 12 to 20, 12 to 25, 12 to 30, 12 to 50, 13 to 20, 13 to 25, 13 to 30, 13 to 50, 14 to 20, 14 to 25, 14 to 30, 14 to 50, 15 to 20, 15 to 25, 15 to 30, 15 to 50, 16 to 18,16 to 20, 16 to 25, 16 to 30, 16 to 50, 17 to 20, 17 to 25, 17 to 30, 17 to 50, 18 to 20, 18 to 25, 18 to 30, 18 to 50, 19 to 20, 19 to 25, 19 to 30, 19 to 50, 20 to 25, 20 to 30, or 20 to 50 linked nucleosides. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets APOE. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2022 / 066956. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2022 / 066956. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2022 / 066956. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets APP. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2022 / 026589. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2022 / 026589. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2022 / 026589. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets ATXN1. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2021 / 222768. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2021 / 222768. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2021 / 222768. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets ATXN2. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2015 / 143246 or WO2020 / 023737. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2015 / 143246 or WO2020 / 023737. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2015 / 143246 or WO2020 / 023737. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets ATXN3. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2018 / 089805, WO2019 / 217708, or WO2020 / 172559. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2018 / 089805, WO2019 / 217708, or WO2020 / 172559. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2018 / 089805, WO2019 / 217708, or WO2020 / 172559. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets C9ORF72. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2016 / 168592. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2016 / 168592. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2016 / 168592. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets GFAP. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2021 / 021673. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2021 / 021673. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2021 / 021673. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets GYS1. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2023 / 122671. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2023 / 122671. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2023 / 122671. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets HTT. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2011 / 032045, WO2011 / 097643, WO2013 / 022984, WO2014 / 059356, or WO2014 / 121287. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2011 / 032045, WO2011 / 097643, WO2013 / 022984, WO2014 / 059356, or WO2014 / 121287. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2011 / 032045, WO2011 / 097643, WO2013 / 022984, WO2014 / 059356, or WO2014 / 121287. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets KCNT1. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2020 / 190740 or WO2021 / 263082. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2020 / 190740 or WO2021 / 263082. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2020 / 190740 or WO2021 / 263082. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets LRRK2. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2020 / 006267. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2020 / 006267. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2020 / 006267. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets PLP1. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2022 / 006134. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2022 / 006134. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2022 / 006134. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets PMP22. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2017 / 156242, WO2020 / 132558, or WO2021 / 258011. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2017 / 156242, WO2020 / 132558, or WO2021 / 258011. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2017 / 156242, WO2020 / 132558, or WO2021 / 258011. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets PRNP. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2020 / 106996. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2020 / 106996. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2020 / 106996. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets SCN1A. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2021 / 174036. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2021 / 174036. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2021 / 174036. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets SMN2. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2018 / 014041 or WO2021 / 174019. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2018 / 014041 or WO2021 / 174019. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2018 / 014041 or WO2021 / 174019. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets SNCA. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2019 / 164562. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2019 / 164562. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2019 / 164562. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets STMN2. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2019 / 241648. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2019 / 241648. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2019 / 241648. In certain embodiments, oligomeric compounds described herein comprise or consists of a modified oligonucleotide consisting of 12 to 50 linked nucleosides, in which a portion of the modified oligonucleotide targets UBE3A-ATS. In certain embodiments, the modified oligonucleotide has a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of any of the nucleobase sequences of oligonucleotides disclosed in WO2020 / 205463. In certain embodiments, the modified oligonucleotide comprises of an oligonucleotide disclosed in WO2020 / 205463. In certain embodiments, the modified oligonucleotide consists of an oligonucleotide disclosed in WO2020 / 205463. X. Certain Methods and Uses Provided herein are pharmaceutical compositions formulated for use to ameliorate or prevent an acute neurotoxicity in a subject. In certain embodiments, the acute neurotoxicity is an acute activation. In certain embodiments, the pharmaceutical composition comprises an amount of a divalent cation in which the amount of a divalent cation ameliorates or prevents an acute neurotoxicity (e.g., an acute activation) in the subject. In certain embodiments, the amount of a divalent cation in the pharmaceutical composition reduces the frequency of an acute activation in the subject. In certain embodiments, the amount of a divalent cation in the pharmaceutical composition decreases the intensity of an acute activation in the subject. In certain embodiments, a subject experiences reduced acute neurotoxicity compared to administration of an analogous pharmaceutical composition not including excess divalent cation, for example, aCSF. In certain embodiments, the amount of a divalent cation in the pharmaceutical composition decreases the duration of an acute activation in the subject. In certain embodiments, the acute activation lasts no more than 120 minutes, no more than 90 minutes, no more than 60 minutes, no more than 50 minutes, no more than 45 minutes, no more than 40 minutes, no more than 35 minutes, no more than 30 minutes, no more than 25 minutes, no more than 20 minutes, no more than 15 minutes, no more than 10 minutes, or no more than 5 minutes in the subject post administration. In certain embodiments, the acute activation lasts no more than 30 minutes. In certain embodiments, the acute activation lasts no more than 25 minutes. In certain embodiments, the acute activation lasts no more than 20 minutes. In certain embodiments, the acute activation lasts no more than 15 minutes. In certain embodiments, the acute activation lasts no more than 10 minutes. In certain embodiments, the subject recovers from an acute activation in 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 60 minutes, 70 minutes, 80 minutes, 90 minutes, 100 minutes, 110 minutes, or 120 minutes post administration. In certain embodiments, the amount of a divalent cation in the pharmaceutical composition prevents an acute activation in the subject. In certain embodiments, the amount of a divalent cation in the pharmaceutical composition minimizes the duration, intensity, and / or frequency of an acute sedation in the subject. In certain embodiments, the amount of a divalent cation in the pharmaceutical composition does not induce an acute sedation in the subject. In certain embodiments, a pharmaceutical composition described herein minimizes the duration, intensity, and / or frequency of an acute activation in a subject. In certain embodiments, the pharmaceutical composition shortens the recovery time after symptom onset. In certain embodiments, a symptom of an acute activation improves or is resolved in 120 minutes, 90 minutes, 60 minutes, 50 minutes, 45 minutes, 40 minutes, 35 minutes, 30 minutes, 25 minutes, 20 minutes, 15 minutes, or 10 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 90 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 60 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 45 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 30 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 15 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 10 minutes post symptom onset. In certain embodiments, the symptom is muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, or seizures. Thus, provided herein are methods of administering a pharmaceutical composition described herein to a subject. In certain embodiment, the subject has a neurodegenerative disease or neurodevelopmental disorder. In certain embodiments, the subject has dementia, a channelopathy, a tauopathy, a synucleinopathy, or a spinocerebellar ataxia. In certain embodiments, the subject has Alexander disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Angelman Syndrome, Charcot-Marie-Tooth disease, epilepsy, Friedreich ataxia, frontotemporal dementia, Huntington’s disease, Lafora disease, Lewy body disease, Parkinson’s disease, Pelizaeus-Merzbacher disease, prion disease, or spinal muscular atrophy. In certain embodiments, the subject is a primate. In certain embodiments, the subject is a human. In certain embodiments, disclosed herein is a method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1, and wherein the subject is a primate. In certain embodiments, the pharmaceutical composition is formulated to ameliorate or prevent an acute neurotoxicity in the subject. In certain embodiments, the acute neurotoxicity is an acute activation. In certain embodiments, the pharmaceutical composition is formulated to reduce the frequency of an acute activation, decrease the duration of an acute activation, and / or decrease the intensity of an acute activation in the subject. In certain embodiments, the acute activation lasts no more than 120 minutes, no more than 90 minutes, no more than 60 minutes, no more than 50 minutes, no more than 45 minutes, no more than 40 minutes, no more than 35 minutes, no more than 30 minutes, no more than 25 minutes, no more than 20 minutes, no more than 15 minutes, no more than 10 minutes, or no more than 5 minutes in the subject post administration. In certain embodiments, the acute activation lasts no more than 30 minutes. In certain embodiments, the acute activation lasts no more than 25 minutes. In certain embodiments, the acute activation lasts no more than 20 minutes. In certain embodiments, the acute activation lasts no more than 15 minutes. In certain embodiments, the acute activation lasts no more than 10 minutes. In certain embodiments, the pharmaceutical composition is formulated to decrease one or more phenotypes associated with an acute activation, e.g., to decrease muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, nystagmus, urinary incontinence, increased muscle cramping or spasms, convulsions, and / or seizures. In certain embodiments, the pharmaceutical composition is formulated to prevent an acute activation in the subject. In certain embodiments, the pharmaceutical composition minimizes the duration, intensity, and / or frequency of an acute sedation in the subject. In certain embodiments, the pharmaceutical composition does not induce an acute sedation in the subject. In certain embodiments, the subject has a neurodegenerative disease or neurodevelopmental disorder, for example, but not limited to, dementia, a channelopathy, a tauopathy, a synucleinopathy, or a spinocerebellar ataxia. In certain embodiments, the subject is a human. In certain embodiments, the subject is 18 years of age or older. In certain embodiments, the subject is a juvenile subject (e.g., a human less than 18 years of age). In certain embodiments, the subject is less than 15 years of age, less than 12 years of age, less than 10 years of age, less than 5 years of age, or less than 2 years of age. In certain embodiments, a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1 minimizes the duration, intensity, and / or frequency of an acute activation in a subject, wherein the subject is a primate. In certain embodiments, the molar ratio of divalent cation to the oligomeric compound is from 2 to 3. In certain embodiments, the pharmaceutical composition shortens the recovery time after symptom onset. In certain embodiments, a symptom of an acute activation improves or is resolved in 120 minutes, 90 minutes, 60 minutes, 50 minutes, 45 minutes, 40 minutes, 35 minutes, 30 minutes, 25 minutes, 20 minutes, 15 minutes, or 10 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 90 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 60 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 45 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 30 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 15 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 10 minutes post symptom onset. In certain embodiments, the symptom is muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, nystagmus, urinary incontinence, increased muscle cramping or spasms, convulsions, or seizures. In certain embodiments, the subject has a neurodegenerative disease or neurodevelopmental disorder, for example, but not limited to, dementia, a channelopathy, a tauopathy, a synucleinopathy, or a spinocerebellar ataxia. In certain embodiments, the subject is a human. In certain embodiments, the subject is 18 years of age or older. In certain embodiments, the subject is a juvenile subject (e.g., a human less than 18 years of age). In certain embodiments, the subject is less than 15 years of age, less than 12 years of age, less than 10 years of age, less than 5 years of age, or less than 2 years of age. In certain embodiments, disclosed herein is a method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1, and wherein the subject is a primate. In certain embodiments, the pharmaceutical composition is formulated to ameliorate or prevent an acute neurotoxicity in the subject. In certain embodiments, the acute neurotoxicity is an acute activation. In certain embodiments, the pharmaceutical composition is formulated to reduce the frequency of an acute activation, decrease the duration of an acute activation, and / or decrease the intensity of an acute activation in the subject. In certain embodiments, the acute activation lasts no more than 120 minutes, no more than 90 minutes, no more than 60 minutes, no more than 50 minutes, no more than 45 minutes, no more than 40 minutes, no more than 35 minutes, no more than 30 minutes, no more than 25 minutes, no more than 20 minutes, no more than 15 minutes, no more than 10 minutes, or no more than 5 minutes in the subject post administration. In certain embodiments, the acute activation lasts no more than 30 minutes. In certain embodiments, the acute activation lasts no more than 25 minutes. In certain embodiments, the acute activation lasts no more than 20 minutes. In certain embodiments, the acute activation lasts no more than 15 minutes. In certain embodiments, the acute activation lasts no more than 10 minutes. In certain embodiments, the pharmaceutical composition is formulated to decrease one or more phenotypes associated with an acute activation, e.g., to decrease muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, nystagmus, urinary incontinence, increased muscle cramping or spasms, convulsions, and / or seizures. In certain embodiments, the pharmaceutical composition is formulated to prevent an acute activation in the subject. In certain embodiments, the pharmaceutical composition minimizes the duration, intensity, and / or frequency of an acute sedation in the subject. In certain embodiments, the pharmaceutical composition does not induce an acute sedation in the subject. In certain embodiments, the subject has a neurodegenerative disease or neurodevelopmental disorder, for example, but not limited to, dementia, a channelopathy, a tauopathy, a synucleinopathy, or a spinocerebellar ataxia. In certain embodiments, the subject is a human. In certain embodiments, the subject is 18 years of age or older. In certain embodiments, the subject is a juvenile subject (e.g., a human less than 18 years of age). In certain embodiments, the subject is less than 15 years of age, less than 12 years of age, less than 10 years of age, less than 5 years of age, or less than 2 years of age. In certain embodiments, a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1 minimizes the duration, intensity, and / or frequency of an acute activation in a subject, wherein the subject is a primate. In certain embodiments, the pharmaceutical composition shortens the recovery time after symptom onset. In certain embodiments, a symptom of an acute activation improves or is resolved in 120 minutes, 90 minutes, 60 minutes, 50 minutes, 45 minutes, 40 minutes, 35 minutes, 30 minutes, 25 minutes, 20 minutes, 15 minutes, or 10 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 90 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 60 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 45 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 30 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 15 minutes post symptom onset. In certain embodiments, the symptom improves or is resolved in 10 minutes post symptom onset. In certain embodiments, the symptom is muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, nystagmus, urinary incontinence, increased muscle cramping or spasms, convulsions, or seizures. In certain embodiments, the subject has a neurodegenerative disease or neurodevelopmental disorder, for example, but not limited to, dementia, a channelopathy, a tauopathy, a synucleinopathy, or a spinocerebellar ataxia. In certain embodiments, the subject is a human. In certain embodiments, the subject is 18 years of age or older. In certain embodiments, the subject is a juvenile subject (e.g., a human less than 18 years of age). In certain ...

Claims

WHAT IS CLAIMED:

1. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.

1.

2. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.

1.

3. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the total concentration of the divalent cation is greater than 2.2 mM.

4. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 3.

5. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the total concentration of the divalent cation is greater than 2.2 mM, and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 3.

6. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and artificial cerebrospinal fluid (aCSF) comprising an excess of a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.

1.

7. The pharmaceutical composition of claim 3, wherein the molar ratio of the divalent cation to the oligomeric compound is from 2 to 7.

1.

8. The pharmaceutical composition of any of claims 1-3, 6, or 7, wherein the molar ratio of the divalent cation to the oligomeric compound is from 2 to 6, 2 to 5.2, 2 to 5, 3 to 6, 3 to 5.2, 3 to 5, 2.3 to 5.2, or 2 to 4.

9. The pharmaceutical composition of any of claims 1-3 or 6-8, wherein the molar ratio of the divalent cation to the oligomeric compound is from 2 to 3.

10. The pharmaceutical composition of any of claims 2, 3, 5, or 6, wherein the concentration of the oligomeric compound is 1.2 mM or higher.

11. The pharmaceutical composition of any of claims 1-10, wherein the concentration of the oligomeric compound is 2 mM or higher, 3 mM or higher, 4 mM or higher, or 5 mM or higher.

12. The pharmaceutical composition of any of claims 1-10, wherein the concentration of the oligomeric compound is from 1.2 mM to 4 mM, from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM,from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM.

13. The pharmaceutical composition of any of claims 1, 2, 4, or 6, wherein the total concentration of the divalent cation is greater than 2.2 mM.

14. The pharmaceutical composition of any of claims 1-13, wherein the total concentration of the divalent cation is 3 mM or higher, 4 mM or higher, 5 mM or higher, 6 mM or higher, 7 mM or higher, 8 mM or higher, 9 mM or higher, 10 mM or higher, or 15 mM or higher.

15. The pharmaceutical composition of any of claims 1-13, wherein the total concentration of the divalent cation is from 2.3 mM to 35 mM, from 2.3 mM to 30 mM, from 2.3 mM to 20 mM, from 2.3 mM to 15 mM, from 2.3 mM to 10 mM, from 2.5 mM to 30 mM, from 2.5 mM to 20 mM, from 2.5 mM to 15 mM, from 2.5 mM to 10 mM, from 3 mM to 30 mM, from 3 mM to 20 mM, from 3 mM to 15 mM, from 3 mM to 10 mM, from 5 mM to 30 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 30 mM, from 10 mM to 20 mM, or from 15 mM to 30 mM.

16. The pharmaceutical composition of any of claims 1-15, wherein the divalent cation is selected from Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, Zn2+, or a combination thereof.

17. The pharmaceutical composition of claim 16, wherein the divalent cation is selected from Ca2+, Mg2+, Zn2+, or a combination thereof.

18. The pharmaceutical composition of claim 16, wherein the divalent cation is selected from Ca2+, Mg2+, or a combination thereof.

19. The pharmaceutical composition of claim 16, wherein the divalent cation is Ca2+.

20. The pharmaceutical composition of claim 16, wherein the divalent cation is Mg2+.

21. The pharmaceutical composition of any of claims 1-20, wherein the pharmaceutically acceptable diluent comprises artificial cerebrospinal fluid (aCSF).

22. The pharmaceutical composition of any of claims 1-20, wherein the pharmaceutically acceptable diluent comprises phosphate-buffered saline (PBS).

23. The pharmaceutical composition of any of claims 1-22, wherein the oligomeric compound comprises a modified oligonucleotide consisting of 12 to 30 linked nucleosides.

24. The pharmaceutical composition of claim 23, wherein the modified oligonucleotide consists of 12 to 20, 12 to 25, 12 to 30, 13 to 20, 13 to 25, 13 to 30, 14 to 20, 14 to 25, 14 to 30, 15 to 20, 15 to 25, 15 to 30, 16 to 18,16 to 20, 16 to 25, 16 to 30, 17 to 20, 17 to 25, 17 to 30, 18 to 20, 18 to 25, 18 to 30, 19 to 20, 19 to 25, 19 to 30, 20 to 25, or 20 to 30 linked nucleosides.

25. The pharmaceutical composition of claim 23 or 24, wherein the modified oligonucleotide consists of 16, 17, 18, 19, or 20 linked nucleosides.

26. The pharmaceutical composition of any of claims 23-25, wherein the modified oligonucleotide consists of 20 linked nucleosides.

27. The pharmaceutical composition of any of claims 1-26, wherein the modified oligonucleotide has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or 20 contiguous nucleobases of SEQ ID NOs: 92- 94.

28. The pharmaceutical composition of any of claims 1-26, wherein the modified oligonucleotide consists of SEQ ID NOs: 92-94.

29. The pharmaceutical composition of any of claims 1-28, wherein the modified oligonucleotide comprises a modified nucleoside.

30. The pharmaceutical composition of claim 29, wherein the modified nucleoside comprises a modified sugar moiety.

31. The pharmaceutical composition of claim 30, wherein the modified sugar moiety comprises a bicyclic sugar moiety.

32. The pharmaceutical composition of claim 31, wherein the bicyclic sugar moiety comprises a 2’-4’ bridge selected from -O-CH2-; and -O-CH(CH3)-.

33. The pharmaceutical composition of claim 30, wherein the modified sugar moiety comprises a non- bicyclic modified sugar moiety.

34. The pharmaceutical composition of claim 33, wherein the non-bicyclic modified sugar moiety is a 2’- MOE sugar moiety, a 2’-OMe sugar moiety, 2’-NMA, or a 2’-β-D-deoxyxylosyl sugar moiety.

35. The pharmaceutical composition of claim 30, wherein the modified sugar moiety comprises a sugar surrogate.

36. The pharmaceutical composition of claim 35, wherein the sugar surrogate is any of morpholino, modified morpholino, glycol nucleic acid (GNA), six-membered tetrahydropyran (THP), and F-hexitol nucleic acid (F-HNA).

37. The pharmaceutical composition of any of claims 1-36, wherein the modified oligonucleotide comprises at least one modified internucleoside linkage.

38. The pharmaceutical composition of claim 37, wherein at least one internucleoside linkage is a phosphodiester internucleoside linkage.

39. The pharmaceutical composition of claim 37 or claim 38, wherein at least one modified internucleoside linkage is a phosphorothioate internucleoside linkage.

40. The pharmaceutical composition of any of claims 37-39, wherein at least one modified internucleoside linkage is a mesyl phosphoramidate internucleoside linkage.

41. The pharmaceutical composition of any of claims 37-40, wherein each internucleoside linkage is independently selected from a phosphodiester internucleoside linkage, a phosphorothioate internucleoside linkage, and a mesyl phosphoramidate internucleoside linkage.

42. The pharmaceutical composition of any of claims 37, 39, or 40, wherein each internucleoside linkage is independently selected from a phosphorothioate internucleoside linkage and a mesyl phosphoramidate internucleoside linkage.

43. The pharmaceutical composition of any of claims 37-39, wherein each internucleoside linkage is independently selected from a phosphodiester internucleoside linkage and a phosphorothioate internucleoside linkage.

44. The pharmaceutical composition of any of claims 37, 39, or 41-43, wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.

45. The pharmaceutical composition of any of claims 1-44, wherein at least one nucleoside of the modified oligonucleotide comprises a modified nucleobase.

46. The pharmaceutical composition of claim 45, wherein the modified nucleobase is a 5-methylcytosine.

47. The pharmaceutical composition of claim 46, wherein each cytosine is a 5-methylcytosine.

48. The pharmaceutical composition of any of claims 1-46, wherein each nucleoside of the modified oligonucleotide is unmodified adenine, unmodified guanine, unmodified thymine, unmodified cytosine, modified adenine, or 5-methylcytosine.

49. The pharmaceutical composition of any of claims 1-48, wherein the modified oligonucleotide comprises a deoxy region.

50. The pharmaceutical composition of claim 49, wherein each nucleoside of the deoxy region is a 2’-β- D-deoxynucleoside.

51. The pharmaceutical composition of claim 49 or claim 50, wherein the deoxy region consists of 6, 7, 8, 9, 10, or 6-10 linked nucleosides.

52. The pharmaceutical composition of any of claims 49-51, wherein each nucleoside immediately adjacent to the deoxy region comprises a modified sugar moiety.

53. The pharmaceutical composition of any of claims 49-51, wherein the deoxy region is flanked on the 5’-side by a 5’-region consisting of 1-6 linked 5’-region nucleosides and on the 3’-side by a 3’-region consisting of 1-6 linked 3’-region nucleosides; wherein at least one nucleoside of the 5’-region comprises a modified sugar moiety; and at least one nucleoside of the 3’-region comprises a modified sugar moiety.

54. The pharmaceutical composition of claim 53, wherein each nucleoside of the 5’-region comprises a modified sugar moiety.

55. The pharmaceutical composition of claim 53 or claim 54, wherein each nucleoside of the 3’-region comprises a modified sugar moiety.

56. The pharmaceutical composition of any of claims 1-55, wherein the oligomeric compound consists of the modified oligonucleotide.

57. The pharmaceutical composition of any of claims 1-55, wherein the oligomeric compound comprises a conjugate group.

58. The pharmaceutical composition of claim 57, wherein the conjugate group comprises a conjugate moiety and a conjugate linker.

59. The pharmaceutical composition of claim 58, wherein the conjugate linker is a phosphodiester linker.

60. The pharmaceutical composition of claim 58, wherein the conjugate linker consists of a single bond.

61. The pharmaceutical composition of any of claims 58-60, wherein the conjugate linker is cleavable.

62. The pharmaceutical composition of any of claims 58, 59, or 61, wherein the conjugate linker comprises 1-3 linker-nucleosides, wherein at least one linker nucleoside is linked to the conjugate moiety, to the modified oligonucleotide, or to another linker-nucleoside by a phosphodiester bond.

63. The pharmaceutical composition of any of claims 58-62, wherein the conjugate group is attached to the modified oligonucleotide at the 5’ end of the modified oligonucleotide.

64. The pharmaceutical composition of any of claims 58-62, wherein the conjugate group is attached to the modified oligonucleotide at the 3’ end of the modified oligonucleotide.

65. The pharmaceutical composition of any of claims 1-61 or 63-64, wherein the oligomeric compound does not comprise linker-nucleosides.

66. The pharmaceutical composition of any of claims 1-65, comprising a terminal group.

67. The pharmaceutical composition of claim 66, wherein the terminal group is an abasic sugar moiety.

68. The pharmaceutical composition of any of claims 1-67, wherein the oligomeric compound is a single- stranded oligomeric compound.

69. The pharmaceutical composition of any of claims 1-68, wherein the oligomeric compound is a single- stranded RNase H agent.

70. The pharmaceutical composition of any of claims 1-68, wherein the oligomeric compound is an antisense compound.

71. The pharmaceutical composition of any of claims 1-67, wherein the oligomeric compound is a splice- modulating oligomeric compound.

72. The pharmaceutical composition of any of claims 1-67, wherein the oligomeric compound is steric- blocking oligomeric compound.

73. The pharmaceutical composition of any of claims 1-67, or 70-72, wherein the pharmaceutical composition further comprises a second oligomeric compound comprising a second modified oligonucleotide, wherein the second oligomeric compound hybridizes to the oligomeric compound to form an oligomeric duplex.

74. The pharmaceutical composition of claim 73, wherein the second modified oligonucleotide consists of 12 to 30 linked nucleosides, and wherein the nucleobase sequence of the second modified oligonucleotide comprises a complementary region of at least 8 nucleobases that is at least 90% complementary to an equal length portion of the modified oligonucleotide.

75. The pharmaceutical composition of claim 73 or claim 74, wherein at least one nucleoside of the second modified oligonucleotide comprises a modified sugar moiety.

76. The pharmaceutical composition of claim 75, wherein the modified sugar moiety of the second modified oligonucleotide comprises a bicyclic sugar moiety.

77. The pharmaceutical composition of claim 76, wherein the bicyclic sugar moiety of the second modified oligonucleotide comprises a 2’-4’ bridge selected from –O-CH2-; and –O-CH(CH3)-.

78. The pharmaceutical composition of claim 75, wherein the modified sugar moiety of the second modified oligonucleotide comprises a non-bicyclic modified sugar moiety.

79. The pharmaceutical composition of claim 78, wherein the non-bicyclic modified sugar moiety of the second modified oligonucleotide is a 2’-MOE sugar moiety, a 2’-F modified sugar moiety, or 2’-OMe modified sugar moiety.

80. The pharmaceutical composition of any of claims 73-79, wherein at least one internucleoside linkage of the second modified oligonucleotide is a modified internucleoside linkage.

81. The pharmaceutical composition of claim 80, wherein at least one modified internucleoside linkage of the second modified oligonucleotide is a phosphorothioate internucleoside linkage.

82. The pharmaceutical composition of any of claims 73-81, wherein at least one internucleoside linkage of the second modified oligonucleotide is a phosphodiester internucleoside linkage.

83. The pharmaceutical composition of any of claims 80-82, wherein at least one internucleoside linkage of the second modified oligonucleotide is a mesyl phosphoramidate internucleoside linkage.

84. The pharmaceutical composition of any of claims 73-83, wherein each internucleoside linkage of the second modified oligonucleotide is independently selected from a phosphodiester internucleoside linkage, a phosphorothioate internucleoside linkage, or a mesyl phosphoramidate internucleoside linkage.

85. The pharmaceutical composition of any of claims 73-84, wherein the second modified oligonucleotide comprises at least one modified nucleobase.

86. The pharmaceutical composition of claim 85, wherein the at least one modified nucleobase of the second modified oligonucleotide is 5-methylcytosine.

87. The pharmaceutical composition of any of claims 73-86, wherein the second modified oligonucleotide comprises a conjugate group.

88. The pharmaceutical composition of claim 87, wherein the conjugate group comprises a conjugate moiety and a conjugate linker.

89. The pharmaceutical composition of claim 88, wherein the conjugate linker consists of a single bond.

90. The pharmaceutical composition of claim 88 or claim 89, wherein the conjugate linker is cleavable.

91. The pharmaceutical composition of any of claims 88 or 90, wherein the conjugate linker comprises 1- 3 linker-nucleosides, wherein at least one linker nucleoside is linked to the conjugate moiety, to the second modified oligonucleotide, or to another linker-nucleoside by a phosphodiester bond.

92. The pharmaceutical composition of any of claims 88-91, wherein the conjugate linker is a phosphodiester linker.

93. The pharmaceutical composition of any of claims 87-92, wherein the conjugate group is attached to the 5’-end of the second modified oligonucleotide.

94. The pharmaceutical composition of any of claims 87-92, wherein the conjugate group is attached to the 3’-end of the second modified oligonucleotide.

95. The pharmaceutical composition of any of claims 87-92, wherein the conjugate group is attached via the 2’ position of a ribosyl sugar moiety at an internal position of the second modified oligonucleotide.

96. The pharmaceutical composition of any of claims 87-95, wherein the conjugate group comprises a C22 alkyl, C20 alkyl, C21 alkyl, C19 alkyl, C18 alkyl, C17 alkyl, C16 alkyl, C15 alkyl, C14 alkyl, C13 alkyl, C12 alkyl, C11 alkyl, C10 alkyl, C9 alkyl, C8 alkyl, C7 alkyl, C6 alkyl, C5 alkyl, C22 alkenyl, C20 alkenyl, C21 alkenyl, C19 alkenyl, C18 alkenyl, C17 alkenyl, C16 alkenyl, C15 alkenyl, C14 alkenyl, C13 alkenyl, C12 alkenyl, C11 alkenyl, C10 alkenyl, C9 alkenyl, C8 alkenyl, C7 alkenyl, C6 alkenyl, or C5 alkenyl.

97. The pharmaceutical composition of any of claims 87-96, wherein the conjugate group comprises a cell-targeting moiety.

98. The pharmaceutical composition of any of claims 73-97, wherein the second modified oligonucleotide comprises a terminal group.

99. The pharmaceutical composition of claim 98, wherein the terminal group is an abasic sugar moiety.

100. The pharmaceutical composition of any of claims 73-99, wherein the modified oligonucleotide comprises a 5’-stabilized phosphate group.

101. The pharmaceutical composition of claim 100, wherein the stabilized phosphate group comprises a cyclopropyl phosphonate or a vinyl phosphonate.

102. The pharmaceutical composition of any of claims 73-101, wherein the total concentration of the divalent cation is lower than 10 mM, lower than 8 mM, lower than 5 mM, or lower than 3 mM.

103. The pharmaceutical composition of any of claims 73-102, wherein the molar ratio of the divalent cation to the oligomeric duplex is from 2 to 7.

1.

104. The pharmaceutical composition of any of claims 73-103, wherein the molar ratio of the divalent cation to the oligomeric duplex is 2 to 6, 2 to 5.2, 2 to 5, 3 to 6, 3 to 5.2, 3 to 5, 2.3 to 5.2, or 2 to 4.

105. The pharmaceutical composition of any of claims 73-103, wherein the molar ratio of the divalent cation to the oligomeric duplex is from 2 to 3.

106. The pharmaceutical composition of any of claims 73-105, wherein the concentration of the oligomeric duplex is 1.2 mM or higher.

107. The pharmaceutical composition of any of claims 73-106, wherein the concentration of the oligomeric duplex is 2 mM or higher, 3 mM or higher, 4 mM or higher, or 5 mM or higher.

108. A pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 0.11*n to 0.37*n, wherein n is the number of anionic phosphate moieties in the modified oligonucleotide.

109. The pharmaceutical composition of claim 108, wherein the total concentration of the divalent cation is greater than 2.2 mM.

110. The pharmaceutical composition of claim 108 or 109, wherein the oligomeric compound has a concentration of 1.2 mM or higher.

111. The pharmaceutical composition of any of claims 108-110, wherein the molar ratio is from 0.12*n to 0.37*n, from 0.13*n to 0.37*n, from 0.15*n to 0.37*n, from 0.2*n to 0.37*n, from 0.3*n to 0.37*n, from 0.12*n to 0.3*n, from 0.12*n to 0.25*n, from 0.12*n to 0.27*n, from 0.15*n to 0.3*n, or from 0.2*n to 0.3*n.

112. The pharmaceutical composition of any of claims 108-111, wherein n is the total number of phosphodiester and phosphorothioate internucleoside linkages, or wherein n is the total number of phosphodiester, phosphorothioate, and mesyl phosphoramidate internucleoside linkages, in the modified oligonucleotide.

113. The pharmaceutical composition of any of claims 108-111, wherein the pharmaceutical composition further comprises a second oligomeric compound comprising a second modified oligonucleotide, wherein the second oligomeric compound hybridizes to the oligomeric compound to form an oligomeric duplex, and n is the total number of phosphodiester and phosphorothioate internucleoside linkages in the first modified oligonucleotide and the second modified oligonucleotide.

114. The pharmaceutical composition of any of claims 108-113, wherein n is from 13 to 19, from 13 to 43, from 17 to 43, from 18 to 43, or from 19 to 43.

115. The pharmaceutical composition of any of claims 108-114, wherein the concentration of the oligomeric compound is from 1.2 mM to 4 mM, from 2 mM to 20 mM, from 2 mM to 15 mM, from 2 mM to 10 mM, from 2 mM to 5 mM, from 5 mM to 20 mM, from 5 mM to 15 mM, from 10 mM to 20 mM, or from 15 mM to 20 mM.

116. The pharmaceutical composition of any of claims 108-115, wherein the divalent cation is selected from Ba2+, Be2+, Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, Ni2+, Zn2+, or a combination thereof.

117. The pharmaceutical composition of claim 116, wherein the divalent cation is selected from Ca2+, Mg2+, Zn2+, or a combination thereof.

118. The pharmaceutical composition of claim 116 or 117, wherein the divalent cation is selected from Ca2+, Mg2+, or a combination thereof.

119. The pharmaceutical composition of claim 118, wherein the divalent cation is Ca2+.

120. The pharmaceutical composition of claim 118, wherein the divalent cation is Mg2+.

121. The pharmaceutical composition of any of claims 108-120, wherein the pharmaceutically acceptable diluent comprises artificial cerebrospinal fluid (aCSF).

122. The pharmaceutical composition of any of claims 108-120, wherein the pharmaceutically acceptable diluent comprises phosphate-buffered saline (PBS).

123. The pharmaceutical composition of any of claims 1-122, wherein the pharmaceutical composition consists essentially of or consists of the oligomeric compound or oligomeric duplex, aCSF, and an excess amount of a divalent cation selected from Ca2+and Mg2+, or a combination thereof.

124. The pharmaceutical composition of any of claims 1-123, wherein the pharmaceutical composition consists essentially of or consists of the oligomeric compound or oligomeric duplex, aCSF, and an excess amount of Ca2+divalent cation.

125. The pharmaceutical composition of any of claims 1-123, wherein the pharmaceutical composition consists essentially of or consists of the oligomeric compound or oligomeric duplex, aCSF, and an excess amount of Mg2+divalent cation.

126. The pharmaceutical composition of any of claims 1-122, wherein the pharmaceutical composition consists essentially of or consists of the oligomeric compound or oligomeric duplex, PBS, and an excess amount of a divalent cation selected from Ca2+and Mg2+, or a combination thereof.

127. The pharmaceutical composition of any of claims 1-122 or 126, wherein the pharmaceutical composition consists essentially of or consists of the oligomeric compound or oligomeric duplex, PBS, and an excess amount of Ca2+divalent cation.

128. The pharmaceutical composition of any of claims 1-122 or 126, wherein the pharmaceutical composition consists essentially of or consists of the oligomeric compound or oligomeric duplex, PBS, and an excess amount of Mg2+divalent cation.

129. Use of a pharmaceutical composition of any of claims 1–128 for treating a neurodegenerative disease or a neurodevelopmental disorder in a subject.

130. Use of a pharmaceutical composition of any of claims 1–128 in the manufacture of a medicament for treating a neurodegenerative disease or a neurodevelopmental disorder in a subject.

131. A method comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition of any of claims 1-128.

132. A method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1, and wherein the subject is a primate.

133. A method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide anda pharmaceutically acceptable diluent comprising a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 7.1, and wherein the subject is a primate.

134. A method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the total concentration of the divalent cation is greater than 2.2 mM and wherein the subject is a primate.

135. A method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the oligomeric compound has a concentration of 1.2 mM or higher, and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 3.

136. A method administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and a pharmaceutically acceptable diluent comprising a divalent cation, wherein the total concentration of the divalent cation is greater than 2.2 mM and wherein the molar ratio of divalent cation to the oligomeric compound is from 2 to 3.

137. A method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an oligomeric compound comprising a modified oligonucleotide and artificial cerebrospinal fluid (aCSF) comprising an excess of a divalent cation, wherein the molar ratio of divalent cation to the oligomeric compound to from 2 to 7.

1.

138. The method or use of any of claims 131-137, wherein the nucleobase sequence of the modified oligonucleotide is at least 80%, 85%, 90%, or 95%, or is 100% complementary to an equal length portion of a target nucleic acid.

139. The method or use of claim 138, wherein the target nucleic acid is expressed in a cell of the central nervous system (CNS).

140. The method or use of claim 139, wherein the target nucleic acid is expressed in a brain cell.

141. The method or use of claim 139, wherein the target nucleic acid is expressed in a neuron.

142. The method or use of claim 139, wherein the target nucleic acid is expressed in a glial cell.

143. The method or use of claim 142, wherein the target nucleic acid is expressed in an oligodendrocyte, an astrocyte, a microglia, or an ependymal cell, or its respective progenitor cell.

144. The method or use of any of claims 138-143, wherein the target nucleic acid is APOE, APP, ATXN1, ATXN2, ATXN3, C9ORF72, GFAP, GYS1, HTT, KCNT1, LRRK2, PLP1, PMP22, PRNP, SCN1A, SMN2, SNCA, STMN2, or UBE3A-ATS.

145. The method or use of any of claims 129-144, wherein the subject has a neurodegenerative disease or a neurodevelopmental disorder.

146. The method or use of claim 145, wherein the neurodegenerative disease or neurodevelopmental disorder is dementia, a channelopathy, a tauopathy, a synucleinopathy, or a spinocerebellar ataxia.

147. The method or use of claim 145, wherein the neurodegenerative disease or neurodevelopmental disorder is Alexander disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Angelman Syndrome, Charcot-Marie-Tooth disease, epilepsy, Friedreich ataxia, frontotemporal dementia, Huntington’s disease, Lafora disease, Lewy body disease, Parkinson’s disease, Pelizaeus-Merzbacher disease, prion disease, or spinal muscular atrophy.

148. The method or use of any of claims 129-147, wherein the subject experiences reduced acute neurotoxicity compared to administration of an analogous pharmaceutical composition not including excess divalent cation, for example aCSF.

149. The method or use of any of claims 129-147, wherein the subject does not experience acute neurotoxicity compared to administration of an analogous pharmaceutical composition not including excess divalent cation, for example aCSF.

150. The method or use of claim 148 or 149, wherein the acute neurotoxicity is an acute activation.

151. The method or use of claim 150, wherein the acute activation following administration of the analogous pharmaceutical composition not including excess divalent cation, for example aCSF, lasts no more than 120 minutes, no more than 90 minutes, no more than 60 minutes, no more than 50 minutes, no more than 45 minutes, no more than 40 minutes, no more than 35 minutes, no more than 30 minutes, no more than 25 minutes, no more than 20 minutes, no more than 15 minutes, no more than 10 minutes, or no more than 5 minutes in the subject post administration.

152. The method or use of claim 150 or 151, wherein a symptom of an acute activation improves or is resolved in 120 minutes, 90 minutes, 60 minutes, 50 minutes, 45 minutes, 40 minutes, 35 minutes, 30 minutes, 25 minutes, 20 minutes, 15 minutes, or 10 minutes post symptom onset.

153. The method or use of claim 152, wherein the symptom is muscle twitching, tremors of the limbs, uncontrolled movements of the limbs, stereotypic movement, hyperactivity, nystagmus, urinary incontinence, increased muscle cramping or spasms, convulsions, or seizures.

154. The method or use of claim 150, wherein the pharmaceutical composition prevents an acute activation in the subject.

155. The method or use of any of claims 129-154, wherein administration of the pharmaceutical composition does not induce an acute sedation in the subject.

156. The method or use of any of claims 129-155, wherein the pharmaceutical composition is administered by intrathecal or intracerebroventricular administration.

157. The method or use of any of preceding claims, wherein the subject is a human.

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