Cell-targeting complexes and uses thereof

Abstract

Provided are transferrin receptor binding VHH domains as well as delivery complexes and methods for targeting cells of interest for delivery of an active cargo such as an oligomeric agent. In particular, the delivery complex may comprise modified Fc domain and a transferrin receptor binding VHH domain.

Description

[0001] CELL-TARGETING COMPLEXES AND USES THEREOF 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 CORE0173WOSEQ.xml created August 12, 2025, which is 252 kb in size. The information in the electronic format of the sequence listing is incorporated herein by reference in its entirety. Field The present embodiments provide transferrin receptor binding proteins and delivery complexes thereof, as well as methods of use thereof. Background The blood brain barrier (BBB), separating systemic circulation from the brain, is formed from specialized endothelial cells that form tight junctions that prevent diffusion of molecules larger than ~500 Da into brain tissue. Transport of larger molecules across the BBB is achieved by receptor-mediated transcytosis (RMT). One of these receptors is the type 1 transferrin receptor (TfR1), also known as CD71, a transmembrane glycoprotein that binds to and internalizes iron-bound transferrin by receptor-mediated endocytosis. TfR1 targeting complexes, including antibodies, antibody fragments, and peptides, have potential to deliver oligonucleotides, cytotoxic drugs, antibodies, and antibody fragments across the BBB into the CNS. Oligomeric agents, including single-stranded oligonucleotides and oligomeric duplexes, such as single-stranded antisense oligonucleotides (ASOs) and siRNA, have been shown to be useful for regulating gene expression and have proven to be therapeutically effective. However, delivery to certain tissues of interest remains an unmet need. Various oligomeric agents for CNS diseases have been FDA-approved or are currently in clinical trials; however, the majority of these drugs are administered directly into the CNS via intrathecal injection, while those administered systemically have very low rates of CNS exposure. Thus, there is a need for systemically delivered therapeutic agents that are capable of crossing the BBB. Summary Embodiments provided herein are directed to novel transferrin receptor binding domains and delivery complexes thereof. The novel transferrin receptor binding domain comprises a VHH (camelid single variable heavy chain) domain that binds to human TfR1. In certain embodiments, a transferrin-receptor binding domain comprises a VHH domain. In certain embodiments, a transferrin receptor binding domain consists of a VHH domain. In certain embodiments, a transferrin receptor binding domain consists of a VHH domain and an N-terminal extension. In certain embodiments, a transferrin receptor binding domain consists of a VHH domain and a C-terminal extension. In certain embodiments, a transferrin receptor binding domain consists of a VHH domain and both an N-terminal extension and a C-terminal extension. Also provided herein are delivery complexes comprising a transferrin receptor binding domain and at least one active cargo. In certain embodiments, the delivery complex further comprises a stabilizing moiety. In certain embodiments, the stabilizing moiety is a protein domain. In certain embodiments, the stabilizing moiety is a modified Fc domain. In certain embodiments, the active cargo is selected from an oligomeric agent, a nucleic acid, a peptide, a polypeptide, a protein, a chromophore, an imaging agent, a small molecule, an antibody or antibody fragment, or a lipid. In certain embodiments, the delivery complex comprises exactly one transferrin receptor binding domain. In certain embodiments, the delivery complex comprises exactly two transferrin receptor binding domains. In certain embodiments, the delivery complex comprises a modified Fc domain that is a dimer. In certain such embodiments, the modified Fc domain is a homodimer. In certain such embodiments, the modified Fc domain is a heterodimer. In certain such embodiments, the modified Fc domain is a knob-in-hole heterodimer. In certain embodiments, the active cargo is an oligomeric agent. In certain embodiments, the oligomeric agent comprises an antisense oligonucleotide. In certain embodiments, the oligomeric agent is an oligomeric duplex comprising an antisense oligonucleotide and a sense oligonucleotide. 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 of the embodiments, as claimed. Herein, the use of the singular includes the plural unless specifically stated otherwise. The use of the term “including” as well as other forms, such as “includes” and “included”, is not limiting. 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, treatises, and GenBank, NCBI, and ENSEMBL reference sequence records are hereby expressly incorporated by reference for the portions of the document discussed herein, as well as in their entirety. It is understood that throughout the specification, the first letter in a peptide sequence is the first amino acid of the peptide at the N-terminus and the last letter in a peptide sequence is the last amino acid of the peptide at the C-terminus unless indicated otherwise. Similarly, the first nucleoside in a nucleotide sequence represents the 5’-end of the nucleotide, and the last letter in the nucleotide sequence represents the 3’ end, unless indicated otherwise. 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 in 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’-deoxy sugar moiety. Unless otherwise indicated, a 2’-deoxynucleoside is a 2’-β-D-deoxynucleoside which comprises a 2’-β-D- deoxyribosyl sugar moiety, which is in the β-D ribosyl configuration as found in naturally occurring deoxyribonucleic acid (DNA). 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’-deoxy sugar moiety” means a 2’-H(H) deoxyfuranosyl sugar moiety. Unless otherwise indicated, a 2’-deoxy sugar moiety is a 2’-β-D-deoxyribosyl sugar moiety, which has the β-D ribosyl stereochemical configuration as found in naturally occurring deoxyribonucleic acids (DNA). As used herein, “2’-MOE” means a 2’-OCH2CH2OCH3group in place of the 2’-OH group of a furanosyl sugar moiety. A “2’-MOE sugar moiety” means a sugar moiety with a 2’-OCH2CH2OCH3group in place of the 2’-OH group of a furanosyl sugar moiety. Unless otherwise indicated, a 2’-MOE sugar moiety is in the β-D-ribosyl stereochemical configuration. “MOE” means O-methoxyethyl. As used herein, “2’-MOE nucleoside” or “2’- OCH2CH2OCH3nucleoside” means a nucleoside comprising a 2’-MOE sugar moiety (or 2’-OCH2CH2OCH3furanosyl sugar moiety). As used herein, “2’-OMe” or “2’-O-methyl” means a 2’-OCH3group in place of the 2’-OH group of a furanosyl sugar moiety. A “2’-OMe sugar moiety” or “2’-O-methyl sugar moiety” means a sugar moiety with a 2’-OCH3group in place of the 2’-OH group of a furanosyl sugar moiety. Unless otherwise indicated, a 2’-OMe sugar moiety is in 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 sugar moiety. As used herein “2’-NMA” means a 2’-OCH2C(=O)-N(H)CH3group in place of the 2’-OH group of a furanosyl sugar moiety. A “2’-NMA sugar moiety” means a sugar moiety with a 2’-OCH2C(=O)-N(H)CH3group in place of the 2’-OH group of a furanosyl sugar moiety. As used herein, “2’-NMA nucleoside” means a nucleoside comprising a 2’-NMA sugar moiety. As used herein, “2’-substituted nucleoside” means a modified nucleoside comprising a 2’-substituted furanosyl sugar moiety. As used herein, “2’-substituted sugar moiety” means a furanosyl sugar moiety wherein at least one 2’-substituent is other than H or OH. A 2’-substituted sugar moiety includes a bicyclic sugar moiety wherein the second ring is joined to the furanosyl ring at the 2’-position. 2’-substituted sugar moieties include, but are not limited to, 2’-OMe sugar moieties, 2’-MOE sugar moieties, 2’-F sugar moieties, cEt sugar moieties, and LNA sugar moieties. As used herein, “5-methyl cytosine” means a cytosine modified with a methyl group attached to the 5 position. A 5-methyl cytosine is a modified nucleobase. As used herein, an “abasic nucleoside” means a modified nucleoside in which the sugar moiety is not attached to a nucleobase. As used herein, an “antigen binding fragment” of a camelid antibody refers to the VHH domain. As used herein, “antisense oligonucleotide” means an oligonucleotide having at least one region which is complementary to a target nucleic acid (a “targeting region”). An antisense oligonucleotide may be paired with a second oligonucleotide (herein, a “sense oligonucleotide”) that is complementary to the antisense oligonucleotide (for example, forming an “oligomeric duplex”), may be an unpaired antisense oligonucleotide (herein, a single-stranded antisense oligonucleotide), or may be a “hairpin oligonucleotide”, which has at least one region that is self-complementary. 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 a furanosyl sugar moiety and a second ring, wherein the second ring is formed via a bridge connecting two atoms in the ring of the furanosyl sugar moiety, thereby forming a bicyclic structure. Examples of bicyclic sugar moieties include locked nucleic acid (LNA) sugar moieties and constrained ethyl (cEt) sugar moieties as defined herein. As used herein, “C-terminus” refers to the carboxylate moiety of a polypeptide main chain, or the CONH2moiety in the case of a C-terminal amidated polypeptide. Fusing another peptide at the C-terminus means that said peptide is attached specifically at this position, rather than at a side chain of the C-terminal amino acid. As used herein, “cell-targeting moiety” means a conjugate group or portion of a conjugate group that has affinity for a particular cell type or particular cell types. For example, a cell-targeting moiety may have affinity for a surface moiety, such as a surface receptor on a particular cell type. A cell-targeting moiety may be capable of being internalized when it interacts with or binds the cell-surface receptor or the cell-surface moiety. In certain embodiments, a cell-targeting moiety is a VHH domain. As used herein, “cell-surface moiety” means a moiety present on the surface of a cell that is available to interact with matter external to the cell. A portion of the cell-surface moiety may be integral with the cell membrane of the cell. Non-limiting examples of cell-surface moieties are lipids, proteins, and carbohydrates. In certain embodiments, a cell-surface moiety is a cell-surface receptor. As used herein, “cell-surface receptor” means a protein receptor expressed on the surface of a cell that is available to interact with a corresponding ligand. The ligand may be endogenous or exogenous. In certain embodiments, the cell-surface receptor is the transferrin receptor. 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, “cleavable moiety” means a group of atoms comprising at least one bond that is cleaved under physiological conditions, that is, in a cell or a subject. For example, a cleavable moiety is cleaved inside a cell or sub-cellular compartment, such as an endosome or lysosome. A cleavable moiety may be cleaved by endogenous enzymes, such as nucleases. As used herein, “complementary nucleobases” means nucleobases that form hydrogen bonds with one another when two strands of linked nucleosides (e.g., an oligonucleotide and a target nucleic acid; or two oligonucleotides) or, alternatively, two regions of a single strand of linked nucleosides (e.g., as in a “hairpin oligonucleotide”) are aligned. Complementary nucleobase pairs include, but are not limited to, 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 are complementary to unmodified nucleobases or to other modified nucleobases are known in the art. For example, hypoxanthine, the nucleobase of the nucleoside inosine (I), can pair with adenine, cytosine, thymine, or uracil. Herein, hypoxanthine (I) is considered a complementary nucleobase to thymine (T), adenine (A), uracil (U), and cytosine (C). As used herein, “complementary” refers to two nucleobase sequences in which some or all of the nucleobases in the two sequences are complementary nucleobases when the sequences are aligned. A “nucleobase sequence” means the order of contiguous nucleobases in a strand of linked nucleosides or a region thereof (e.g., an oligonucleotide or region thereof, or a target nucleic acid or region thereof) independent of any sugar or internucleoside linkage modification. Each of the two nucleobase sequences may be a sequence corresponding to the nucleobase sequence of any strand of linked nucleosides or region thereof. For example, complementary nucleobase sequences may be the nucleobase sequences of two separate strands of linked nucleosides or region thereof (e.g., an oligonucleotide and a region of a target nucleic acid, or an antisense oligonucleotide and its paired sense oligonucleotide) or complementary nucleobase sequences may be two regions of a single strand of linked nucleosides (e.g., self-complementary regions of a hairpin oligonucleotide). As used herein, when a first strand of linked nucleosides (e.g., an oligonucleotide) or region thereof is described as being complementary to a second strand of linked nucleosides or region thereof (e.g., a target nucleic acid or another oligonucleotide), it means that the nucleobase sequence of the first strand of linked nucleosides or region thereof is complementary to the nucleobase sequence of the second strand of linked nucleosides or region thereof. Not every pair of nucleobases in the aligned nucleobase sequences needs to be complementary for the two sequences to be “complementary.” Rather, some mismatches are tolerated. Where complementarity is expressed as a percent, such percent represents the percent of nucleobases within one nucleobase sequence that are complementary to nucleobases within an equal length second sequence when the sequences are aligned. Unless otherwise specified, “complementary” is assumed to be at least 70%. Complementary nucleobase sequences may be 75%, 80%, 85%, 90%, 95%, or 100% complementary. For example, if the nucleobase sequence of an oligonucleotide consisting of 20 nucleosides is 80% complementary to another nucleobase sequence, then 16 of the nucleobase pairs are complementary nucleobases, and there are 4 mismatches when the sequences are aligned. If the nucleobase sequence of an oligonucleotide consisting of 20 nucleosides is at least 80% complementary to another nucleobase sequence, then 16, 17, 18, 19, or 20 of the nucleobase pairs are complementary nucleobases, and there are 0-4 mismatches when the sequences are aligned. As used herein, “fully complementary” or “100% complementary” means that each nucleobase pair of the two nucleobase sequences is complementary when the equal length sequences are aligned. As used herein, "contiguous" in the context of a polymer refers to polymeric subunits that are immediately adjacent to each other. For example, in the context of an oligonucleotide, “contiguous” 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. For example, in the context of a peptide or protein, two amino acids are said to be “contiguous” when they are consecutive in a linear sequence; that is, no additional amino acids or other chemical entities are present between the two amino acids. As used herein, “delivery complex” means a composition comprising at least one active cargo and least one cell-targeting moiety. The active cargo may be an oligomeric agent. The cell-targeting moiety may be a transferrin receptor binding domain, such as a VHH domain. The delivery complex may further comprise a stabilization moiety. As used herein, “deoxy region” means a region of 5-12 contiguous nucleosides, wherein at least 70% of the nucleosides are DNA nucleosides. Each nucleoside of the deoxy region is selected from a 2’- deoxynucleoside and 2’-substituted nucleoside. A deoxy region supports RNase H activity. As used herein, “dimeric” in the context of polypeptides refers to two polypeptides that are linked together, e.g., through side chains, typically via a Cys-Cys disulfide bond. As used herein, a “heterodimer” is a dimer formed between two polypeptides with distinct peptide sequences, such as two distinct Fc polypeptide sequences. As used herein, a “homodimer” is a dimer formed between two polypeptides having the same peptide sequence, such as two identical Fc polypeptide sequences. A homodimer may be further modified by enzymatic or chemical methods to introduce a linker, cell-targeting moiety, and / or an active cargo attached to an amino acid side chain or N- or C-terminus. A cell-targeting moiety and / or active cargo may include a second peptide or polypeptide. This is still considered a homodimer unless the polypeptide sequences differ apart from the linker, cell-targeting moiety, and / or active cargo. As used herein, “DNA nucleoside” means a nucleoside comprising an unmodified DNA sugar moiety. A DNA nucleoside may be abasic or comprise a modified or unmodified nucleobase. In some embodiments, a DNA nucleoside may comprise a uracil nucleobase or a modified nucleobase. As used herein, “DNA sugar moiety” means an unmodified DNA sugar moiety. As used herein, “double-stranded” refers to paired complementary regions, including those between two separate strands of linked nucleosides (e.g., an antisense oligonucleotide and a sense oligonucleotide) and those within a single strand of linked nucleosides (e.g., a hairpin oligonucleotide). Paired complementary regions of two separate strands of linked nucleosides form a duplex of the separate strands. Paired complementary regions of a single strand of linked nucleosides form a “hairpin”. As used herein, “duplex” means a structure formed by two separate strands of linked nucleosides or regions thereof (e.g., two separate oligonucleotides), at least a portion of which are complementary to and hybridize to each other. For clarity, herein a “hairpin oligonucleotide” is a single strand of linked nucleosides that comprises a region that is double stranded and is not a duplex. As used herein, “Fc domain” means a protein domain corresponding to a fragment of an antibody containing the CH2 and CH3 domains, and optionally an N-terminal extension comprising no more than 62 amino acids, preferably comprising no more than 15 amino acids. An “Fc domain” is a dimer of two “Fc polypeptides”. In certain embodiments, an Fc domain is derived from papain digestion of a human IGG1 antibody and contains the CH2 and CH3 domains as well as a portion of the hinge region. An unmodified Fc domain may be a homodimer of any of SEQ ID NO: 37-42. A “modified Fc domain” comprises two Fc polypeptides each comprising a polypeptide with a sequence with at least 75% identity to any of SEQ ID NO: 4-9, and optionally 1-62 additional amino acids at the N-terminus, wherein the Fc domain is not a homodimer of two polypeptides with 100% sequence identity to any of SEQ ID NO: 37-42. A modified Fc polypeptide may have at least 95% sequence identity to an equal length portion of any of SEQ ID NO: 4-9, and the equal length portion is at least 30, at least 50, at least 100, at least 150, or at least 200 amino acids in length. As used herein, “identity,” or “percent identity”, with regards to an amino acid sequence or nucleic acid sequence, means the percentage of amino acids or nucleobases that are identical between two sequences when the sequences are aligned for maximal similarity. Percent identity for polypeptides can be determined by a program such as BLASTp (Altschul, et al., J. Mol. Biol., 1990; Altschul, et al., Nucleic Acids Research, 1997) or Clustal Omega (Sievers, et al., Molecular Sys.Biol., 2011; Goujon et al., Nucleic Acids Research, 2010; McWilliam, et al., Nucleic Acids Research 2013). Percent identity for nucleotides can be determined by a program such as BLASTn(Altschul, et al., J. Mol. Biol., 1990; Altschul, et al., Nucleic Acids Research, 1997). As used herein, the term “internucleoside linkage” means the covalent linkage between adjacent nucleosides in an oligonucleotide. As used herein, “modified internucleoside linkage” means any internucleoside linkage other than a phosphodiester internucleoside linkage. A “phosphorothioate 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. A “mesyl phosphoramidate internucleoside linkage” is a modified internucleoside linkage in which one of the non-bridging oxygen atoms of a phosphodiester internucleoside linkage is replaced with NS(=O)2CH3. Unless otherwise indicated, and in the context of linked nucleosides each comprising a furanosyl sugar moiety, an internucleoside linkage joins the 3’-carbon of one furanosyl sugar moiety to the 5’-carbon of the other furanosyl sugar moiety. 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, “N-terminus” refers to the terminal amino moiety of a polypeptide main chain. Fusing another peptide at the N-terminus means that said peptide is attached specifically at this position, rather than at a side chain of the N-terminal amino acid. As used herein, “nucleoside” means an “unmodified nucleoside” or a “modified nucleoside”. As used herein, an “unmodified nucleoside” means a compound or subunit comprising an unmodified sugar moiety and an unmodified nucleobase. As used herein, a “modified nucleoside” means a compound or subunit comprising a sugar moiety and optionally a nucleobase, wherein the sugar moiety is modified and / or the nucleobase is modified or absent. As used herein, a “mismatch” is a nucleobase of a first strand of linked nucleosides or region thereof that is not complementary with the corresponding nucleobase of a second strand of linked nucleosides or region thereof when the first and second strands of linked nucleosides are aligned. As used herein, “modified sugar moiety” means a group of atoms other than an unmodified sugar moiety that forms the portion of a nucleoside corresponding to the β-D-ribosyl sugar in RNA or the β-D- deoxyribosyl sugar in DNA. A modified sugar moiety is selected from a modified furanosyl sugar moiety, a cyclic sugar surrogate, an acyclic sugar surrogate, or a sugar mimic. 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, “nucleobase” means an unmodified nucleobase or a modified nucleobase. A nucleobase is a heterocyclic moiety. 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 forming at least one hydrogen bond with at least one other nucleobase. A “5-methyl cytosine” 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” or “the sequence of” a reference nucleobase 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, “the peptide sequence of” or “the polypeptide sequence of” or “the sequence of” a reference peptide / polypeptide SEQ ID NO refers to the linear, amide-bond-linked amino acid sequence provided in such SEQ ID NO, even in cases where the given peptide or polypeptide contains one or more modified side chains that that link to another moiety. As used herein, “oligonucleotide” means a strand of linked nucleosides, wherein each nucleoside and / or internucleoside linkage of the strand of linked nucleosides may be independently modified or unmodified. Unless otherwise indicated, oligonucleotides consist of 12-50 linked nucleosides. Unless otherwise indicated, no more than 10% of the nucleosides of an oligonucleotide are abasic nucleosides. As used herein, “modified oligonucleotide” means an oligonucleotide, wherein at least one nucleoside and / or internucleoside linkage is modified. As used herein, “unmodified oligonucleotide” means an oligonucleotide consisting of unmodified nucleosides linked by phosphodiester internucleoside linkages. An oligonucleotide may be paired with a second oligonucleotide that is complementary to the oligonucleotide to form an oligomeric duplex, or it may be unpaired. As used herein, “pharmaceutically acceptable carrier or diluent” means an ingredient in a pharmaceutical composition suitable for use in administering to a subject. Typically, a “carrier” or “diluent” lacks pharmacological activity but is desirable in preparing a pharmaceutical composition. 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 administration to a subject. As used herein “prodrug” means a therapeutic agent in a first form outside the body that is converted to a second form within an animal or cells thereof. Typically, conversion of a prodrug within the animal is facilitated by the action of an enzyme (e.g., endogenous or viral enzyme) or chemical present in cells or tissues and / or by physiologic conditions. The first form of the prodrug may be less active than the second form. As used herein, “reactive group” means an atom or group of atoms of an amino acid that can form bonds with another compound, e.g., another atom or group of atoms of another amino acid or another compound. A reactive group may be the sulfur atom of a cysteine amino acid. As used herein, “RNAi agent” or “siRNA agent” means an antisense agent that acts, at least in part, through RISC or Ago2 to modulate a target nucleic acid and / or 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 terminal groups and / or linkers. 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 principally 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 terminal groups and / or linkers. 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, “splice-modulating agent” means an antisense agent that acts, at least in part, by modulating the splicing of a target nucleic acid. A “splice-modulating” agent comprises a “splice-modulating oligonucleotide”. As used herein, “steric-blocking agent” means an antisense agent 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 moiety” means a 5’-phosphate analog that is metabolically more stable than a 5’-phosphate as naturally occurs on DNA or RNA. As used herein, “stabilization moiety” means a chemical entity that either (a) has substantial plasma half-life, e.g. albumin or an Fc domain or (b) binds to an endogenous moiety that has substantial plasma half- life, e.g. serum albumin. A stabilization moiety may be a modified Fc domain. 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 absolute stereochemical configuration of a chiral center can be controlled by using stereochemically-pure starting materials, e.g., using β-D-ribosyl nucleoside monomers for oligonucleotide synthesis. In contrast, 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 stereorandom chiral center may not be racemic because one absolute configuration predominates following synthesis, e.g., due to the action of non-chiral reagents near the enriched stereochemistry of an adjacent sugar moiety. The stereorandom chiral center may be at the phosphorous atom of a stereorandom phosphorothioate or stereorandom mesyl phosphoramidate internucleoside linkage. As used herein, “subject” means a human or a non-human animal. The subject may be a human. 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 are furanosyl or deoxyfuranosyl sugar moieties in the β-D-ribosyl stereochemical configuration, and have one hydrogen at each of the 1’, 3’, and 4’ positions, an oxygen at the 3’ position, two hydrogens at the 5’ position and two hydrogens (DNA) or a hydrogen and an OH (RNA) at the 2’ position. As used herein, “sugar mimic” means a group of atoms forming the portion of a nucleoside corresponding to the β-D-ribosyl sugar in RNA other than a modified furanosyl sugar moiety, a cyclic sugar surrogate, or an acyclic sugar surrogate. As used herein, "sugar surrogate" means an acyclic sugar surrogate or cyclic sugar surrogate as described herein below. As used herein, “target nucleic acid” and “target RNA” mean an endogenous nucleic acid that an oligonucleotide is complementary to and intended to affect. Target RNA means an RNA transcript and includes pre-mRNA and mRNA unless otherwise specified. As used herein, “target region” means a portion of a target nucleic acid to which an oligonucleotide is designed to hybridize. As used herein, a “targeting region” is a “complementary region” that is complementary to target region of a target nucleic acid. As used herein, “complementary region” in reference to a first strand of linked nucleosides (e.g., an oligonucleotide or a nucleic acid) is the range of nucleobases of the first strand of linked nucleosides that is complementary with a second strand of linked nucleosides. A “complementary region” may include a mismatch, but the terminal nucleobases of a “complementary region” of the first strand of linked nucleosides are complementary to the second strand of linked nucleosides. 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, “transferrin receptor”, “TfR1”, and “CD71” mean the mammalian type 1 transferrin receptor. “Human transferrin receptor” and “human TfR1” means the protein encoded by the gene represented by ENSEMBL ID ENSG00000072274 (SEQ ID NO: 1) and / or GenBank ID the complement of NC_000003.12 truncated from nucleotides 196016001 to 196085000 (SEQ ID NO: 2) and / or GenBank Gene ID 7037. “Mouse transferrin receptor” and “mouse TfR1” means the protein encoded by the gene represented by ENSEMBL ID ENSMUSG00000022797 (SEQ ID NO: 56) and / or GenBank ID NC_000082.6 truncated from nucleotides 32606001 to 32636000 (SEQ ID NO: 57) and / or GenBank Gene ID 22042. As used herein, “transferrin receptor binding moiety” means a ligand that binds to a mammalian type 1 transferrin receptor. As used herein, “treating” means improving a subject’s disease, condition, or predisposition by administering a delivery complex including a cargo, such as an oligomeric agent, 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. CERTAIN EMBODIMENTS The present disclosure provides the following non-limiting numbered embodiments: Embodiment 1. A polypeptide comprising a VHH domain that binds transferrin receptor (TfR), wherein the VHH domain comprises: CDR1 comprising the amino acid sequence of SEQ ID NO: 14 with no more than 2 substitutions or no more than 1 substitution; CDR2 comprising the amino acid sequence of SEQ ID NO: 16 with no more than 2 substitutions or no more than 1 substitution; and CDR3 comprising the amino acid sequence of SEQ ID NO: 18 with no more than 2 substitutions or no more than 1 substitution; OR CDR1 comprising the amino acid sequence of SEQ ID NO: 24 with no more than 2 substitutions or no more than 1 substitution; CDR2 comprising the amino acid sequence of SEQ ID NO: 26 with no more than 2 substitutions or no more than 1 substitution; and CDR3 comprising the amino acid sequence of SEQ ID NOs: 28 with no more than 2 substitutions or no more than 1 substitution. Embodiment 2. The polypeptide of embodiment 1, wherein the VHH domain comprises: CDR1 comprising the amino acid sequence of SEQ ID NO: 14; CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and CDR3 comprising the amino acid sequence of SEQ ID NO: 18; Or CDR1 comprising the amino acid sequence of SEQ ID NOs: 24; CDR2 comprising the amino acid sequence of SEQ ID NOs: 26; and CDR3 comprising the amino acid sequence of SEQ ID NOs: 28. Embodiment 3. The polypeptide of embodiment 1 or embodiment 2, wherein the VHH domain has at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to SEQ ID NO: 11 or 12. Embodiment 4. The polypeptide of embodiment 1 or embodiment 2, wherein the VHH domain has at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to SEQ ID NO: 21 or 22. Embodiment 5. The polypeptide of any one of embodiments 1-4, consisting of the VHH domain. Embodiment 6. The polypeptide of any one of embodiments 1-4, wherein the polypeptide comprises an N-terminal extension. Embodiment 7. The polypeptide of any one of embodiments 1-4 and 6, wherein the polypeptide comprises a C-terminal extension. Embodiment 8. The polypeptide of embodiment 6 or 7, wherein the N-terminal extension and / or the C-terminal extension comprises a reactive moiety. Embodiment 9. The polypeptide of embodiment 8, wherein the reactive moiety is a free cysteine. Embodiment 10. The polypeptide of any of embodiments 1-4 or 6-9, wherein the polypeptide comprises a Fc polypeptide. Embodiment 11. The polypeptide of embodiment 10, wherein the VHH domain is attached at its N- terminus to the C-terminus of the Fc polypeptide. Embodiment 12. The polypeptide of embodiment 10, wherein the VHH domain is attached at its C- terminus to the N-terminus of the Fc polypeptide. Embodiment 13. The polypeptide of embodiment 10, wherein the VHH domain is attached at its N- terminus to a side chain of the Fc polypeptide. Embodiment 14. The polypeptide of embodiment 10, wherein the VHH domain is attached at its C- terminus to a side chain of the Fc polypeptide. Embodiment 15. The polypeptide of any one of embodiments 10-14, wherein the VHH domain is directly attached to the f Fc polypeptide. Embodiment 16. The polypeptide of any one of embodiments 10-14, wherein the VHH domain is attached through a linker to the Fc polypeptide. Embodiment 17. The polypeptide of any one of embodiments 1-4 or 6-16, wherein the polypeptide comprises one or two VHH domains. Embodiment 18. A polypeptide dimer comprising a first polypeptide and a second polypeptide, wherein the first polypeptide is a polypeptide of any one of embodiments 11-16 comprising a first Fc polypeptide and the second polypeptide comprises a second Fc polypeptide. Embodiment 19. The polypeptide dimer of embodiment 18, wherein the polypeptide dimer comprises exactly one VHH domain. Embodiment 20. The polypeptide dimer of embodiment 18, wherein the sequence of the first Fc polypeptide is identical to the sequence of the second Fc polypeptide. Embodiment 21. The polypeptide dimer of embodiment 18, wherein the sequence of the first Fc polypeptide and the sequence of the second Fc polypeptide are different. Embodiment 22. The polypeptide dimer of embodiment 21, wherein the first Fc polypeptide and the second Fc polypeptide form a knob-in-hole heterodimer. Embodiment 23. The polypeptide dimer of any one of embodiments 18-22, wherein the first Fc polypeptide comprises a sequence having at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 44. Embodiment 24. The polypeptide dimer of any one of embodiments 18-22, wherein the second Fc polypeptide comprises a sequence having at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 44. Embodiment 25. The polypeptide dimer of any of embodiments 18-22, wherein at least one Fc polypeptide has at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% sequence identity to any of SEQ ID NO: 4-9 or 35-44. Embodiment 26. The polypeptide dimer of any of embodiments 18-22, wherein each Fc polypeptide has at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% sequence identity to any of SEQ ID NO: 4-9 or 35-44. Embodiment 27. The polypeptide dimer of any one of embodiments 18-26, wherein the second polypeptide does not comprise an antigen binding domain. Embodiment 28. The polypeptide dimer of any one of embodiments 18-26, wherein the second polypeptide comprises a VHH domain that binds TfR Embodiment 29. The polypeptide dimer of any one of embodiments 18-28, which is a heterodimer. Embodiment 30. The polypeptide dimer of any one of embodiments 18, 20, 23-26 or 28, which is a homodimer. Embodiment 31. The polypeptide dimer of any one of embodiments 18-30, wherein the second polypeptide is a polypeptide of any one of embodiments 10-16, and wherein the first polypeptide and the second polypeptide are the same or different. Embodiment 32. The polypeptide dimer of any of embodiments 18-31, wherein neither Fc polypeptide comprises a transferrin receptor binding moiety. Embodiment 33. A delivery complex comprising a polypeptide of any of embodiments 1-17 or the polypeptide dimer of any one of embodiments 18-32, and at least one cargo. Embodiment 34. The delivery complex of embodiment 33, wherein the cargo is selected from an oligomeric agent, a peptide, a protein, a chromophore, a small molecule, an antibody or antibody fragment, or a lipid. Embodiment 35. The delivery complex of embodiment 33 or 34, wherein the cargo is an oligomeric agent comprising at least one modified oligonucleotide. Embodiment 36. The delivery complex of embodiment 35, wherein the at least one modified oligonucleotide is covalently attached to the VHH domain. Embodiment 37. The delivery complex of any one of embodiments 35-36, wherein the delivery complex comprises exactly one modified oligonucleotide. Embodiment 38. The delivery complex of any one of embodiments 35-36, wherein the delivery complex comprises a second modified oligonucleotide. Embodiment 39. The delivery complex of embodiment 38, wherein the second modified oligonucleotide is covalently attached to the VHH domain. Embodiment 40. The delivery complex of embodiment 38 or 39, wherein the second modified oligonucleotide forms a duplex with the first modified oligonucleotide. Embodiment 41. The delivery complex of any one of embodiments 33-40 having a ratio of two VHH domains to one oligomeric agent. Embodiment 42. The delivery complex of any one of embodiments 33-40 having a ratio of one oligomeric agent to one VHH domain. Embodiment 43. The delivery complex of any one of embodiments 33-40, having a ratio of two oligomeric agents to one VHH domain. Embodiment 44. The delivery complex of any one of embodiments 33-43, wherein the at least one modified oligonucleotide is covalently attached to the first and / or second Fc polypeptide. Embodiment 45. The delivery complex of embodiment 44, wherein the delivery complex comprises exactly one modified oligonucleotide. Embodiment 46. The delivery complex of embodiment 45, wherein the delivery complex comprises a second modified oligonucleotide. Embodiment 47. The delivery complex of embodiment 46, wherein the second modified oligonucleotide is covalently attached to the first Fc polypeptide. Embodiment 48. The delivery complex of embodiment 46 or 47, wherein the second modified oligonucleotide forms a duplex with the first modified oligonucleotide. Embodiment 49. The delivery complex of any of embodiments 46-48, having a ratio of one oligomeric agent to one modified Fc domain . Embodiment 50. The delivery complex of any of embodiments 46-49, having a ratio of two oligomeric agents to one modified Fc domain. Embodiment 51. The delivery complex of any of embodiments 33-49, wherein the at least one modified oligonucleotide is attached to the polypeptide or polypeptide dimer of any of embodiments 1-32 through a click reaction. Embodiment 52. The delivery complex of embodiment 51, wherein the at least one modified oligonucleotide is attached to an Fc domain through a glutamine, optionally Q76, based on the numbering of SEQ ID NO: 51. Embodiment 53. The delivery complex of any of embodiments 33-52, wherein the first modified oligonucleotide consists of 15-30 linked nucleosides. Embodiment 54. The delivery complex of any of embodiments 33-53, wherein the first modified oligonucleotide comprises a targeting region comprising at least 12 contiguous nucleosides, wherein the nucleobase sequence of the targeting region is at least 80% complementary to the nucleobase sequence of an equal-length target region of a target nucleic acid, and wherein the sugar moiety of at least one nucleoside of the first modified oligonucleotide is a modified sugar moiety and / or at least one internucleoside linkage of the first modified oligonucleotide is a modified internucleoside linkage. Embodiment 55. The delivery complex of embodiment 54, comprising a second modified oligonucleotide, wherein the second oligonucleotide consists of 15-30 linked nucleosides. Embodiment 56. The delivery complex of embodiment 54 or 55, wherein the first and / or second modified nucleoside comprises a modified sugar moiety. Embodiment 57. The delivery complex of embodiment 56, wherein the modified sugar moiety comprises a bicyclic sugar moiety. Embodiment 58. The delivery complex of embodiment 57, wherein the bicyclic sugar moiety comprises a 2’-4’ bridge selected from -O-CH2-; and -O-CH(CH3)-. Embodiment 59. The delivery complex of any of embodiments 56-58, wherein the modified nucleoside comprises a non-bicyclic modified sugar moiety. Embodiment 60. The delivery complex of embodiment 59, wherein the non-bicyclic modified sugar moiety is a 2’-MOE sugar moiety, a 2’-OMe sugar moiety, or a 2’-F sugar moiety. Embodiment 61. The delivery complex of any of embodiments 56-60, wherein the modified nucleoside comprises a sugar surrogate. Embodiment 62. The delivery complex of any of embodiments 58-61, wherein the first and / or second modified oligonucleotide comprises at least one modified internucleoside linkage. Embodiment 63. The delivery complex of embodiment 62, wherein at least one modified internucleoside linkage is a phosphorothioate internucleoside linkage or a mesyl phosphoramidate internucleoside linkage. Embodiment 64. The delivery complex of any of embodiments 62-63, wherein each internucleoside linkage is independently selected from a phosphodiester internucleoside linkage, a phosphorothioate internucleoside linkage, and a mesyl phosphoramidate internucleoside linkage. Embodiment 65. The delivery complex of any of embodiments 62-64, wherein at least one nucleoside of the modified oligonucleotide comprises a modified nucleobase. Embodiment 66. The delivery complex of embodiment 65, wherein the modified nucleobase is a 5- methylcytosine. Embodiment 67. The delivery complex of any of embodiments 54-66, wherein the first and / or the second modified oligonucleotide comprises a deoxy region. Embodiment 68. The delivery complex of embodiment 67, wherein each nucleoside of the deoxy region is a 2’-β-D-deoxynucleoside. Embodiment 69. The delivery complex of embodiment 67 or embodiment 68, wherein the deoxy region consists of 6, 7, 8, 9, 10, or 6-10 linked nucleosides. Embodiment 70. The delivery complex of any of embodiments 67-69, wherein each nucleoside immediately adjacent to the deoxy region comprises a modified sugar moiety. Embodiment 71. The delivery complex of any of embodiments 67-70, 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 72. The delivery complex of embodiment 71, wherein each nucleoside of the 5’-region comprises a modified sugar moiety. Embodiment 73. The delivery complex of embodiment 71 or embodiment 72, wherein each nucleoside of the 3’-region comprises a modified sugar moiety. Embodiment 74. The delivery complex of embodiment 55, wherein the second modified oligonucleotide comprises a duplexing region comprising at least 12 contiguous nucleosides, wherein the nucleobase sequence of the duplexing region is at least 80% complementary to the nucleobase sequence of an equal length sequence of the first modified oligonucleotide. Embodiment 75. The delivery complex of embodiment 74, wherein the nucleobase sequence of the duplexing region of the second modified oligonucleotide is at least 85%, at least 90%, at least 95%, or 100% complementary to the nucleobase sequence of an equal length sequence of the first modified oligonucleotide. Embodiment 76. The delivery complex of embodiment 74 or 75, wherein the second modified oligonucleotide consists of the duplexing region. Embodiment 77. The delivery complex of any one of embodiments 74-76, wherein each sugar moiety of the first modified oligonucleotide and the second modified oligonucleotide is selected from a 2’-F sugar moiety, a 2’-OMe sugar moiety, a DNA sugar moiety, a 2’-NMA sugar moiety, a 2’-MOE sugar moiety, and a FHNA sugar surrogate. Embodiment 78. The delivery complex of embodiment 77, wherein the first modified oligonucleotide consists of 23 linked nucleosides and the second modified oligonucleotide consists of 21 linked nucleosides. Embodiment 79. The delivery complex of embodiment 78, wherein the nucleosides at position 2 and the nucleoside at position 14 of the first modified oligonucleotide, counting from the 5’-end, comprise 2’-F sugar moieties. Embodiment 80. The delivery complex of embodiment 78, wherein at least 2 of the nucleosides at positions 7, 9, 10, and 11 of the second modified oligonucleotide, counting from the 5’-end, comprise 2’-F sugar moieties. Embodiment 81. The delivery complex of embodiment 79 or 80, wherein at least 50%, at least 60%, at least 70%, at least 75%, or at least 80% of the nucleosides of the first modified oligonucleotide and / or the second modified oligonucleotide comprise a 2’-OMe sugar moiety. Embodiment 82. The delivery complex of embodiment 79 or 80, wherein fewer than 20%, fewer than 15%, or fewer than 10% of the nucleosides of the first modified oligonucleotide and / or the second modified oligonucleotide comprise a 2’-F sugar moiety. Embodiment 83. The delivery complex of any of embodiments 74-82, wherein the first modified oligonucleotide comprises a stabilized phosphate group attached to the 5’-terminal nucleoside. Embodiment 84. The delivery complex of embodiment 83, wherein the stabilized phosphate group comprises an (E)-vinyl phosphonate. Embodiment 85. The delivery complex of any of embodiments 58-78 or 83-84, wherein the first and / or second modified oligonucleotide consists of 12-30, 12-22, 12-20,14-18, 14-20, 15-17, 15-25, 16-20, 18-22, 19-21, 21-23, or 18-20 linked nucleosides. Embodiment 86. An isolated nucleic acid that encodes the polypeptide of any one of embodiments 1- 17. Embodiment 87. An expression vector comprising the isolated nucleic acid of embodiment 86. Embodiment 88. A host cell comprising the nucleic acid of embodiment 86 or the expression vector of embodiment 87. Embodiment 89. A method of producing the polypeptide of any one of embodiments 1-17, comprising incubating the host cell of embodiment 88 under conditions suitable to express the polypeptide. Embodiment 90. The method of embodiment 89, further comprising isolating the polypeptide. Embodiment 91. An isolated nucleic acid comprising a first polynucleotide sequence encoding the first polypeptide of the polypeptide dimer of any one of embodiments 18-32 and a second polynucleotide sequence encoding the second polypeptide of the polypeptide dimer of any one of embodiments 18-32. Embodiment 92. An expression vector comprising the nucleic acid of embodiment 91. Embodiment 93. A host cell comprising the nucleic acid of embodiment 91 or the expression vector of embodiment 92. Embodiment 94. A host cell that expresses the polypeptide dimer of any one of embodiments 18-32. Embodiment 95. A method of producing the polypeptide dimer of any one of embodiments 18-32, comprising incubating the host cell of embodiment 93 or embodiment 94 under conditions suitable to express the polypeptide dimer. Embodiment 96. The method of embodiment 95, further comprising isolating the polypeptide dimer. Transferrin receptor binding VHH domains Transferrin Receptor The type 1 transferrin receptor (TfR1), also known as CD71 is a transmembrane glycoprotein that binds to and internalizes iron-bound transferrin by receptor-mediated endocytosis. Anti-TfR1 antibodies and antibody fragments have potential to deliver antibodies, antibody fragments, cytotoxic small molecules, oligonucleotides, and enzymes across the blood brain barrier into the CNS. In certain embodiments, the cell-targeting moiety is a transferrin receptor binding moiety. Several examples of transferrin receptor binding moieties have potential for use in delivery complexes for both muscle and nerve (e.g., peripheral and CNS) delivery of various cargoes. Representative cargoes include antibodies and antibody fragments, small molecules, oligonucleotides, and enzymes. Niewoehner, et al. recognized that monovalent binding to the transferrin receptor is required for cargo to cross the blood brain barrier and to avoid degradation of cell surface TfR and down regulation of TfR expression (Niewoehner, et al., Neuron, 2014). Transferrin receptor binding moieties that have been utilized in CNS targeting complexes include antibodies (see, e.g., Sonoda, et al., Pharmaceutics, 2022; Boado, et al., Pharmaceutics, 2022; Georgieva, et al., Pharmaceutics, 2022); engineered Fc domains (see, e.g. US 2020 / 0223935; Ullman, et al. Sci. Transl. Med., 2020; van Lengerich, et al., Nature Neuroscience, 2022; Kariolis, et al., Sci. Transl. Med.2020); Fabs (see, e.g., Weber, et al., Cell Reports, 2018; Yu, et al, Sci. Transl. Med., 2011), scFv domains (see e.g. , Roshanbin, et al., Pharmaceutics, 2022), camelid VHH domains (see, e.g., Wouters, et al., Fluids Barriers CNS, 2020; Su, et al., PLOS ONE, 2022), shark VNAR domains (see e.g. Stocki, et al., FASEB Journal, 2021; Clarke, Pharmaceutics, 2022; US 11,512,136), linear peptides (see, e.g., Lee, et al, Eur. J. Biochem, 2001), cyclic peptides (see, e.g., Staquicini, JCI, 2010; WO2021 / 167107; WO2022 / 101633), and aptamers (see, e.g., US2021 / 0332363; US2022 / 0396794; Zhang et al., Int. J. Mol. Sci., 2021). Transferrin Receptor Binding VHH Domains In certain embodiments, the transferrin receptor binding domain is capable of interacting with the type 1 transferrin receptor. In certain embodiments, transferrin receptor binding domain is capable of binding the type 1 transferrin receptor. In certain embodiments, the transferrin receptor is expressed at the blood- brain barrier. In certain embodiments, the transferrin receptor is expressed in endothelial cells, pericytes and / or astrocytes. In certain embodiments, the transferrin receptor binding domain is capable of binding the type 1 transferrin receptor while not interfering with the binding of the natural ligand transferrin. In certain embodiments, the transferrin receptor binding domain binds an epitope outside of the binding domain of transferrin. In certain embodiments, the transferrin receptor binding domain does not cause dimerization of the type 1 transferrin receptor. In certain embodiments, a transferrin receptor binding domain is capable of being internalized when it interacts with or binds the transferrin receptor. In certain embodiments, a transferrin receptor binding domain is capable of delivering an active cargo to a cell when it interacts with or binds the transferrin receptor. Provided herein are VHH domains that bind to transferrin receptor, wherein the VHH domain comprises CDR1 comprising the amino acid sequence of SEQ ID NO: 14 with no more than 2 substitutions or no more than 1 substitution; CDR2 comprising the amino acid sequence of SEQ ID NO: 16 with no more than 2 substitutions or no more than 1 substitution; and CDR3 comprising the amino acid sequence of SEQ ID NO: 18 with no more than 2 substitutions or no more than 1 substitution; or CDR1 comprising the amino acid sequence of SEQ ID NO: 24 with no more than 2 substitutions or no more than 1 substitution; CDR2 comprising the amino acid sequence of SEQ ID NO: 26 with no more than 2 substitutions or no more than 1 substitution; and CDR3 comprising the amino acid sequence of SEQ ID NOs: 28 with no more than 2 substitutions or no more than 1 substitution. In certain embodiments, the VHH domain comprises CDR1 comprising the amino acid sequence of SEQ ID NO: 14; CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and CDR3 comprising the amino acid sequence of SEQ ID NO: 18; or CDR1 comprising the amino acid sequence of SEQ ID NOs: 24; CDR2 comprising the amino acid sequence of SEQ ID NOs: 26; andCDR3 comprising the amino acid sequence of SEQ ID NOs: 28. In certain embodiments, the VHH domain is a polypeptide having the formula FR1-CDR1-FR2- CDR2-FR3-CDR3-FR4 and / or consisting of polypeptides having the formula NX-FR1-CDR1-FR2-CDR2- FR3-CDR3-FR4-CX, wherein each of FR1, FR2, FR3, and FR4 represent a framework region sequence of a VHH derived from a camelid IGH gene, optionally modified as described herein; each of CDR1, CDR2, and CDR3 represent a complementarity-determining region sequence of a VHH derived from a camelid IGH gene, optionally modified as described herein; and NX and CX represent optional N-terminal and C-terminal extensions, respectively. In certain embodiments, NX is absent. In certain embodiments, NX is a signal sequence. In certain embodiments, NX comprises a reactive group. In certain embodiments, CX is absent. In certain embodiments, CX comprises a purification tag, e.g., a 6X His tag. In certain embodiments, CX comprises a reactive group. In certain embodiments, the reactive group is the thiol of a cysteine amino acid. In certain embodiments, the VHH domain comprises a transferrin receptor binding moiety. In certain embodiments, the VHH domain is VHH-B1 (SEQ ID NO: 11 or SEQ ID NO: 12 or VHH-C7 (SEQ ID NO: 21 or SEQ ID NO: 22). In certain embodiments, VHH-B1 is encoded by the nucleic acid sequence SEQ ID NO: (52) or SEQ ID NO: (53). In certain embodiments, VHH-C71 is encoded by the nucleic acid sequence SEQ ID NO: (54) or SEQ ID NO: (55). Framework regions (FR) and complementarity-determining regions (CDR) can be identified by alignment of the expressed nucleotide sequence with a reference immunoglobulin gene, such as an alpaca IGHV gene. This identification can be obtained by using the IGMT / V-QUEST software available at imgt.org / IMGT_vquest (Brochet, et al., Nuc. Acids. Res.2008; Guidicelli, et al., Cold Spring Harbor Protoc. 2011). Regions in the table below were identified using IGMT / V-QUEST program version 3.6.1 and reference directory release 202329-3, both updated on July 19, 2023. Table 1: VHH-B1 Sequences Region Numbering Sequence SEQ ID based on NO: Table 2: Framework and CDR regions of VHH-C7 Region Numbering Sequence SEQ ID based on NO: SEQ ID Provided herein are delivery complexes comprising a transferrin receptor binding domain and at least one active cargo. In certain embodiments, the active cargo is selected from an oligomeric agent, a nucleic acid, a peptide, a polypeptide, a protein, a chromophore, an imaging agent, a small molecule, an antibody or antibody fragment, or a lipid. In certain embodiments, the active cargo is an oligomeric agent. In certain embodiments, the oligomeric agent comprises an antisense oligonucleotide. In certain embodiments, the oligomeric agent is an oligomeric duplex comprising an antisense oligonucleotide and a sense oligonucleotide. In certain embodiments, the transferrin receptor binding domain is a VHH domain having the formula NX-FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4-CX, described herein above. In certain embodiments, the delivery complex comprises exactly one transferrin receptor binding VHH domain. In certain embodiments, the delivery complex comprises exactly two transferrin receptor binding VHH domains. In certain embodiments, a delivery complex comprises a transferrin receptor binding domain, at least one active cargo, and a stabilizing moiety. In certain embodiments, the active cargo is selected from an oligomeric agent, a nucleic acid, a peptide, a polypeptide, a protein, a chromophore, an imaging agent, a small molecule, an antibody or antibody fragment, or a lipid. In certain embodiments, the active cargo is an oligomeric agent. In certain embodiments, the oligomeric agent comprises an antisense oligonucleotide. In certain embodiments, the oligomeric agent is an oligomeric duplex comprising an antisense oligonucleotide and a sense oligonucleotide. In certain embodiments, the transferrin receptor binding domain is a VHH domain having the formula NX-FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4-CX, described herein above. In certain embodiments, the delivery complex comprises exactly one transferrin receptor binding VHH domain. In certain embodiments, the delivery complex comprises exactly two transferrin receptor binding VHH domains. In certain embodiments, the delivery complex further comprises a stabilizing moiety. In certain embodiments, the stabilizing moiety is a protein domain. In certain embodiments, the stabilizing moiety is a modified Fc domain. In certain embodiments, the modified Fc domain is a dimer. In certain such embodiments, the modified Fc domain is a homodimer. In certain such embodiments, the modified Fc domain is a heterodimer. In certain such embodiments, the modified Fc domain is a knob-in-hole heterodimer. Modified Fc Domains In certain embodiments, the modified Fc domain comprises a first Fc polypeptide and a second Fc polypeptide. In certain embodiments, the modified Fc domain is a homodimer. In certain embodiments, the transferrin receptor binding VHH domain is covalently linked to at least one Fc polypeptide through a side chain of the Fc polypeptide. In certain embodiments, the transferrin receptor binding VHH domain is appended at the N-terminus or C-terminus of at least one Fc polypeptide, optionally attached through a linker. In these embodiments, transferrin receptor binding VHH domain is attached to the active cargo and the active cargo is attached to the Fc polypeptide. In certain such embodiments, the transferrin receptor binding VHH domain is covalently attached to the active cargo and the active cargo is covalently attached to a side chain of the Fc polypeptide. An Fc polypeptide includes, at a minimum, CH2 and CH3 domains, and may include additional hinge region amino acids, or, for certain Ig subtypes, the CH4 domain. An Fc domain is a dimer, and may be a homodimer or a heterodimer. In certain embodiments, the sequences of selected hinge regions and CH2- CH3 domains, as well as complete Fc polypeptides, are shown in the table below. Accession numbers are from the IMGT database, IMGT / LIGM-DB, version 1.2.9, database release LIGMDB_V12 (Giuidicelli, et al, Nucleic Acids Res., 2006). Table 3: Selected human hinge regions and Fc domains IMGT SEQ Accession Human Re ion Se uenceID O 9 0 1 2 4 EPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK 5 6 EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR Hinge- EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP 7 8 9 0 1 2 3 4 ISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVD K RW NVF VMHEALHNHYT K L L P LL P %, at least 90%, at least 95%, or at least 98% sequence identity to any of SEQ ID NO: 4-9. In certain embodiments, the polypeptide comprises a region having at least at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% sequence identity to any of SEQ ID NO: 4-9, and further comprises an N-terminal extension. In certain embodiments, the N-terminal extension has at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% sequence identity to any of SEQ ID NO: 29-34, wherein the C-terminal-most amino acid of the N-terminal extension corresponds to the C-terminal-most amino acid the selected SEQ ID NO(s): 29-34. In certain embodiments, the N- terminal extension consists of the C-terminal-most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acids of any of SEQ ID NO: 29-34. In certain embodiments, the polypeptide has at least 95% sequence identity to an equal length portion of any of SEQ ID NO: 4-9 and the equal length portion is at least 30, at least 50, at least 100, at least 150, or at least 200 amino acids in length. Modified Fc polypeptides can be numbered according to the EU numbering scheme for antibodies (Edelman, et al., PNAS, 1969), which is based on human IGG1 (SEQ ID NO: 51). In the EU numbering scheme for the heavy chain constant region, the hinge region corresponds to amino acids 216-230, the CH2 corresponds to amino acids 231-340, and the CH3 domain corresponds to amino acids 341-446. In certain embodiments, the modified Fc domain is a homodimer. In certain embodiments, the modified Fc domain is not a knob-in-hole heterodimer. In certain embodiments, the modified Fc domain is a heterodimer. In certain embodiments, the modified Fc domain is a knob-in-hole heterodimer. A knob-in-hole heterodimer comprises a first Fc polypeptide having “knob” modifications and a second Fc polypeptide having “hole” modifications. In certain embodiments, “knob” modifications include T336Y. In certain embodiments, “hole” modifications include T366S, L368A and Y407V. In certain embodiments, the modified Fc domain is a homodimer comprising two Fc polypeptides each having “hole” modifications. The Fc domain may comprise one or more other modifications or substitutions. Modifications to Fc polypeptides to modify antibody effector function and other properties have been previously described in detail (see, e.g., Saunders, et al., Front. Immunol., Vol.10: Article 1296, 2019). Antibody effector function of a delivery complex can be reduced to avoid unwanted immune-mediated side effects. This is addressed with certain modifications to naturally-occurring Fc polypeptides. Modifications described below are described relative to the Eu numbering scheme (Reference SEQ ID NO: 51 (hIGG1); Edelman, et al., PNAS, 1969). The so-called ‘LALA’ double modification (Leu234Ala together with Leu235Ala, based EU numbering, or the numbering of SEQ ID NO: 51) was first described as a valuable isotype with diminished effector functions (Lund, J. et al., Mol. Immunol., 1992 (29), 53–59; Tamm , A. and Schmidt , R.E. Int. Rev. Immunol., 1997 (16) , 57 –85), and may be incorporated into any Fc polypeptide of the present invention. P329G reduces binding to C1q, and the combination of P329G and L234A / L235A (“LALA-PG”) eliminates binding to FcγRI, II, III and C1q (Schlothauer, et. al., Protein Engineering, Design and Selection, 29(10):457-466, 2016). Various other modifications have been tested in IgG1-based scaffolds, and have been shown to modulate antibody effector function, including FcγRI, II, III and C1q binding, and / or to modulate antibody pharmacokinetics. The native Fc linked N-glycosylation site can be removed by modification of N297, and interactions with FcγRI are also influenced by P238, D265, A327, and P329 (Jefferis , R. and Lund, J. Immunol. Lett., (2002) 82 , 57-65. Position 235 has also been substituted with glutamic acid (Alegre, M.L. et al. J. Immunol., (1992), 148, 3461-3468). When introduced into the lower hinge and CH2 domain of human IgG1 molecules, the triple modification L234F / L235E / P331S (`TM’) causes a profound decrease in their binding to human CD64, CD32A, CD16 and C1q (Oganesyan, V., et al., Acta. Crystallogr. D Biol. Crystallogr., (2008), 64, 700 –704). In certain embodiments, modifications selected from P329G, P329A, L234A / L235A (“LALA”), N297D, and / or S228P / L235E (numbering relative to SEQ ID NO: 51), may be incorporated into the Fc polypeptide. Modifications to a native IgG1 Fc polypeptide that reduce effector functions and may be incorporated into Fc polypeptides as described herein include, but are not limited to, N297A, N297G, N297Q, L235E, L234A / L235A “LALA”, P331S / L234E / L235F, D265A, G237A, E318A, E233P, G236R / L238R, A330L, D270A, K322A, P329A, P331A, V264A, F241A (numbering relative to SEQ ID NO:51). Modifications to a native IgG2 Fc polypeptide (SEQ ID NO: 5) that reduce effector functions and may be incorporated into Fc polypeptides as described herein include, but are not limited to, H268Q / V309L / A330S / P331S, V234A / G237A / P238S / H268A / V309L / A330S / P331S, based on EU numbering. Modifications to a native IgG4 Fc polypeptide (SEQ ID NO: 7) that reduce effector functions and may be incorporated into Fc polypeptides as described herein include, but are not limited to, S228P / L235E and S228 / F234A / L235E, based on EU numbering (see Wang, et al., Protein Cell, 9(1):63-73, 2018 and Chiu, et al., Antibodies 8:55, 2019). Modifications to a native IgG1 Fc polypeptide that modulate antibody pharmacokinetics include, but are not limited to M252Y / S254T / T256E “YTE”, M428L / N434S, T250Q, M252Y, I253A, S254T, T256E, P257I, T307A, D376V, E380A, M428L, N434S, N434A, N434H, N434F, H435A, H435R, T250Q / M428L, and T307A / E380A / N434A. S228P / L235E, S228 / F234A / L235E (see Wang, et al., Protein Cell, 9(1):63-73, 2018 and Chiu, et al., Antibodies 8:55, 2019). In addition to modifications that modulate antibody pharmacokinetics, the Fc polypeptide may have one or more modifications or substitutions to create an attachment site for a linker or cargo (see, e.g., Agarwal and Bertozzi, Bioconjugate Chemistry, 2014; Tien, et al, PNAS, 2014; Zhou, et al., Biomedicines, 2017; Zhou, Molecules, 2023; Zheng, et al, Angewandte Chem. Int. Ed, 2022). In certain embodiments, a modification is the introduction of a surface Cys. In certain embodiments, a modification is the introduction of an enzymatic recognition sequence within the sequence of the Fc polypeptide (see, e.g., Table 2 of Yamazaki, et al., ChemistrySelect, 2022). In certain embodiments, the sequence is LLQG and the enzyme is MTGase (see Strop, et al., Chemistry and Biology, 2013). In certain embodiments, the LLQG sequence is included in the Fc polypeptide such that the glutamine (Q) is located at a position corresponding to any of positions 222-223, 251-254, 252-253, 222-223, 293-297, 294-297, 295, 297, or 385 of a hIGG1 (Reference SEQ ID NO: 35). In certain embodiments, the glutamine is located at a position corresponding to position 295 of an hIGG1 (SEQ ID NO: 51). In certain embodiments, the LLQG sequence is appended as part of a C- terminal extension at the C-terminus of the CH3 domain. In certain embodiments, the C-terminal lysine K447 is deleted, and a C-terminal extension comprising a LLQG sequence is added at the C-terminus. The modified Fc domain may comprise an Fc polypeptide having a length of 100-600 amino acids, 100-500 amino acids, 100-400 amino acids, 100-300 amino acids, 100-250 amino acids, 150-600 amino acids, 150-500 amino acids, 150-400 amino acids, 150-300 amino acids, 150-250 amino acids, 200-600 amino acids, 200-500 amino acids, 200-400 amino acids, 200-300 amino acids, 200-250 amino acids, 200- 225 amino acids, 210-225 amino acids, 215-225 amino acids, 215-230 amino acids, 215-235 amino acids, 215-240 amino acids, 215-250 amino acids, 225-230 amino acids, 225-240 amino acids, 225-250 amino acids, 225-300 amino acids, 250-300 amino acids amino acids. Preferably, an Fc polypeptide has a length of 200-250 amino acids, or 215-235 amino acids. Certain Cargo In certain embodiments, the oligomeric agent comprises a single-stranded modified oligonucleotide. In certain embodiments, the oligomeric agent is a duplex comprising two complementary modified oligonucleotides. In certain embodiments, an oligomeric agent comprises a modified oligonucleotide and a linker. In certain embodiments, a modified oligonucleotide is covalently attached to an Fc polypeptide through a linker covalently attached to the 5’-end of the oligonucleotide. In certain embodiments, a modified oligonucleotide is covalently attached to an Fc polypeptide through a linker covalently connected to the 3’- end of the oligonucleotide. In certain embodiments, a modified oligonucleotide is not directly attached to an Fc polypeptide. In certain such embodiments, a modified oligonucleotide attached to a transferrin receptor binding VHH domain through a linker covalently connected to the 3’-end of the oligonucleotide. In certain such embodiments, a modified oligonucleotide is covalently attached to a transferrin receptor binding VHH domain through a linker covalently attached to the 5’-end of the oligonucleotide. In certain embodiments, an modified oligonucleotide is covalently attached to an Fc polypeptide and / or a transferrin receptor binding VHH domain at an internal position, for instance, the 2’-position of a furanosyl sugar moiety or through a modified internucleoside linkage. In certain embodiments, the oligomeric agent comprises an antisense oligonucleotide. In certain embodiments, the oligomeric agent is an oligomeric duplex comprising an antisense oligonucleotide and a sense oligonucleotide. In certain embodiments, the oligomeric agent is an RNAse H agent. In certain embodiments, the oligomeric agent is an RNAi agent. Certain Delivery Complexes In certain embodiments, a delivery complex comprises at least one transferrin receptor binding VHH domain, at least one active cargo, and at least one stabilizing moiety. In certain embodiments, the stabilizing moiety is a modified Fc domain. In certain embodiments, the active cargo is an oligomeric agent. In certain embodiments, the number of active cargo attached to one modified Fc domain forms a ratio, which is the ratio of oligomeric agents per modified Fc domain. In certain embodiments, the ratio of active cargo to modified Fc domain is about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or greater. In some instances, the ratio of the active cargo to modified Fc domain is about 1 or greater. In some instances, the ratio the active cargo to modified Fc domain is about 2 or greater. In some instances, the ratio of the active cargo to modified Fc domain is about 3 or greater. In some instances, the ratio of the active cargo to modified Fc domain is about 4 or greater. In some instances, the ratio of the active cargo to modified Fc domain is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16. In some instances, the ratio of the active cargo to modified Fc domain is 1. In some instances, the ratio of the active cargo to modified Fc domain is 2. In some instances, the ratio of the active cargo to modified Fc domain is 4. In certain embodiments, the number of transferrin receptor binding VHH domains associated with one modified Fc domain forms a ratio, which is the ratio transferrin receptor binding VHH domains per modified Fc domain. In certain embodiments, a transferrin receptor binding VHH domain is covalently attached to a modified Fc domain. In these embodiments, the ratio of transferrin receptor binding VHH domains to modified Fc domains is about 0.5, 1, 2, 3, 4, 5, 6, 7, 8 or greater. In some instances, the ratio of transferrin receptor binding VHH domains to modified Fc domain is about 0.5 or lower. In some instances, the ratio of transferrin receptor binding VHH domains to modified Fc domain is about 1 or lower. In some instances, the ratio of transferrin receptor binding VHH domains to modified Fc domain is about 0.5 or greater. In some instances, the ratio of transferrin receptor binding VHH domains to modified Fc domain is about 1 or greater. In some instances, the ratio of transferrin receptor binding VHH domains to modified Fc domain is about 2 or greater. In some instances, the ratio of the In some instances, the ratio of transferrin receptor binding VHH domains to modified Fc domain is about 3 or greater. In some instances, the ratio of the In some instances, the ratio of transferrin receptor binding VHH domains to modified Fc domain is about is about 4 or greater. In some instances, the ratio of transferrin receptor binding VHH domains to modified Fc domain is about is 0.5, 1, 2, 3, 4, 5, 6, 7, or 8. In some instances, the ratio of transferrin receptor binding VHH domains to modified Fc domain is 0.5. In some instances, the ratio of transferrin receptor binding VHH domains to modified Fc domain is 1. In some instances, the ratio of transferrin receptor binding VHH domains to modified Fc domain is 2. In certain embodiments, the number of transferrin receptor binding VHH domains associated with one oligomeric agent forms a ratio, which is the ratio of transferrin receptor binding VHH domains per oligomeric agent. In certain embodiments, the ratio of transferrin receptor binding VHH domains to oligomeric agents is about 0.05, 0.1, 0.2, 0.25, 0.3, 0.4, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or greater. In some instances, the ratio of transferrin receptor binding VHH domains to oligomeric agent is about 0.5 or lower. In some instances, the ratio of transferrin receptor binding VHH domains to oligomeric agent is about 1 or lower. In some instances, the ratio of transferrin receptor binding VHH domains to oligomeric agent is about 1 or greater. In some instances, the ratio of transferrin receptor binding VHH domains to oligomeric agent is about 2 or greater. In some instances, the ratio of transferrin receptor binding VHH domains to oligomeric agent is about 3 or greater. In some instances, the ratio of transferrin receptor binding VHH domains moiety to oligomeric agent is about 4 or greater. In some instances, the ratio of transferrin receptor binding VHH domains to oligomeric agent is 0.05, 0.1, 0.2, 0.25, 0.3, 0.4, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16. In some instances, the ratio of transferrin receptor binding VHH domains to oligomeric agent is 0.5. In some instances, the ratio of the transferrin receptor binding VHH domains to oligomeric agent is 1. In some instances, the ratio of the transferrin receptor binding VHH domains to oligomeric agent is 2. In certain embodiments, a delivery complex includes a modified Fc domain comprising a first Fc polypeptide and a second Fc polypeptide, at least one transferrin receptor binding VHH domain, and at least one oligomeric agent. In certain embodiments, the modified Fc domain is a homodimer. In certain embodiments, the transferrin receptor binding VHH domain is attached to the first Fc polypeptide and / or the second Fc polypeptide via an amino acid side chain, optionally via a linker. In certain embodiments, the transferrin receptor binding VHH domain is appended at the N-terminus or the C-terminus of the first Fc polypeptide and / or the second Fc polypeptide, optionally via a linker. In certain embodiments, the delivery complex is capable of interacting with the type 1 transferrin receptor. In certain embodiments, the delivery complex is capable of binding the type 1 transferrin receptor. In certain embodiments, the transferrin receptor is expressed at the blood-brain barrier. In certain embodiments, the delivery complex is capable of binding the type 1 transferrin receptor while not interfering with the binding of the natural ligand transferrin. In certain embodiments, the delivery complex does not cause dimerization of the type 1 transferrin receptor. In certain embodiments, a delivery complex is capable of being internalized when it interacts with or binds the transferrin receptor. In certain embodiments, a delivery complex is capable of delivering an active cargo to a cell when it interacts with or binds the transferrin receptor. In certain embodiments, the active cargo is an oligomeric agent. In certain embodiments, the oligomeric agent is a single stranded modified oligonucleotide. In certain such embodiments, the modified oligonucleotide is covalently attached to the first and / or the second Fc polypeptide via an amino acid side- chain optionally via a linker. In certain such embodiments, the modified oligonucleotide is covalently attached to the N-terminus or C-terminus of the first and / or second Fc polypeptide. In certain embodiments, the 5’-end of the modified oligonucleotide is attached to the Fc polypeptide. In certain embodiments, the 3’- end of the modified oligonucleotide is attached to the Fc polypeptide. In certain embodiments, the modified oligonucleotide is covalently attached to the transferrin receptor binding VHH domain. In certain such embodiments, the oligonucleotide is covalently attached to the transferrin receptor binding VHH domain through an amino acid side-chain. In certain such embodiments, the oligonucleotide is covalently attached to the transferrin receptor binding VHH domain through the N-terminus or C-terminus thereof. In certain embodiments, the oligomeric agent is an oligomeric duplex comprising an antisense oligonucleotide and a sense oligonucleotide. In certain embodiments, the antisense oligonucleotide is covalently attached to the first and / or second Fc polypeptide via an amino acid side-chain. In certain embodiments, the antisense oligonucleotide is covalently attached to the N-terminus or C-terminus of the first and / or second Fc polypeptide. In certain embodiments, the 5’-end of the antisense oligonucleotide is attached to the Fc polypeptide. In certain embodiments, the 3’-end of the antisense oligonucleotide is attached to the Fc polypeptide. In certain embodiments, the 5’-end of the sense oligonucleotide is attached to the Fc polypeptide. In certain embodiments, the 3’-end of the sense oligonucleotide is attached to the Fc polypeptide. In certain embodiments, the antisense oligonucleotide is covalently attached to the transferrin receptor binding VHH domain. In certain such embodiments, the antisense oligonucleotide is covalently attached to the transferrin receptor binding VHH domain through an amino acid side-chain. In certain such embodiments, the antisense oligonucleotide is covalently attached to the transferrin receptor binding VHH domain through the N-terminus or C-terminus. In certain embodiments, the 5’-end of the antisense oligonucleotide is attached to the transferrin receptor binding VHH domain. In certain embodiments, the 3’- end of the antisense oligonucleotide is attached to the transferrin receptor binding VHH domain. In certain embodiments, the sense oligonucleotide is covalently attached to a transferrin receptor binding VHH domain. In certain such embodiments, the sense oligonucleotide is covalently attached to the transferrin receptor binding VHH domain through a side-chain. In certain such embodiments, the sense oligonucleotide is covalently attached to the transferrin receptor binding VHH domain through the N- terminus or C-terminus. In certain embodiments, the 5’-end of the sense oligonucleotide is attached to the transferrin receptor binding VHH domain. In certain embodiments, the 3’-end of the sense oligonucleotide is attached to the transferrin receptor binding VHH domain. Certain Linkers In certain embodiments, delivery complexes consist of macromolecules joined together by linkers. In certain embodiments, the first macromolecule is an oligomeric agent comprising a modified oligonucleotide. In certain embodiments, a second macromolecule comprises or consists of a polypeptide. In certain embodiments, the polypeptide is a modified Fc domain. In certain embodiments, the polypeptide is a transferrin receptor binding VHH domain. In certain embodiments, the linker comprises a chain structure, such as a hydrocarbyl chain, or an oligomer of repeating units such as ethylene glycol. In certain embodiments, the linker comprises a cleavable moiety. In certain embodiments, the linker comprises a phosphodiester group. In certain embodiments, the linker comprises a triazole group. In certain embodiments, the linker comprises a tetrazole group. In certain embodiments, the linker comprises a disulfide group. In certain embodiments, linkers are bifunctional linking moieties, e.g., those known in the art to be useful for attaching two larger molecules to each other. In general, a bifunctional linking moiety comprises at least two functional groups. One of the functional groups is selected to react with a particular site on one of the two molecules and the other is selected to react with a particular site on the second molecule. 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, azido, hydroxyl, carboxylic acid, thiol, alkyl, alkenyl, and alkynyl. In certain embodiments, linkers comprise chemical groups that are formed upon a reaction between a first functional group and a second functional group. In certain embodiments, a modified oligonucleotide is attached to the first functional group during synthesis. In certain embodiments, a second functional group is present on a macromolecule to be attached to the modified oligonucleotide. Then, the two compounds containing the first functional group and the second functional group are mixed under specific conditions to yield the final complex. In certain embodiments, the second functional group is present on a polypeptide. In certain embodiments, the polypeptide comprises or consists of a modified Fc domain. In certain embodiments, the polypeptide comprises or consists of a transferrin receptor binding VHH domain. In certain embodiments, a second functional group is introduced into the polypeptide via an enzymatic reaction. In certain embodiments, the second functional group is introduced into the polypeptide during chemical synthesis. Certain such reactions that are compatible with both oligonucleotide and peptide chemistry have been previously described and are often called “bioconjugation” reactions. These reactions include strain promoted azido-alkyne cycloaddition (SPAAC), copper-catalyzed click reaction (CuAAC), active ester conjugation to an amino modified oligonucleotide, maleimide-thiol Michael addition, ketol / hydroxylamine ligation, the Staudinger ligation, reductive amination, thio ether formation, disulfide formation, reductive alkylation, catalyst-free N-arylation, sulfur fluoride exchange click reaction (SuFEx), and inverse demand Diels Alder reaction. Certain such reactions are described in, e.g., Jbara, et al., “Oligonucleotide Bioconjugation with Bifunctional Palladium Reagents”, Angew. Chem. Int. Ed.2021, 60(21)12109-12115; Dong, et al., “Sulfur(VI) Fluoride Exchange (SuFEx): Another Good Reaction for Click Chemistry,” Angew. Chem. Int. Ed.2014, 53(36):9430-9448.4; Zhang, et al., “Arylation Chemistry for Bioconjugation,” Angew. Chem. Int. Ed. Engl.2019; 58(15): 4810–4839; Walsh, et al., “Site-selective modification strategies in antibody-drug conjugates” Chem. Soc. Rev., 2021, 50: 1305-1353; Tiefenbrunn, et al., “Chemoselective ligation techniques: modern applications of time-honored chemistry”, Biopolymers, 2010, 94(1):95-106; Drake, et al., Bioconjug. Chem.2014, 25(7):1331-1341; Bode, Acc. Chem. Res., 2017, 50, 9, 2104–2115; J. Magano, B. Bock, et al, Org. Proc. Res. Dev.2014, 18:142-151; Craig S. McKay and M.G. Finn, “Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation”, Chemistry & Biology 2014; Mitchell P. Christy et al., Org. Lett.2020, 22: 2365; Ren et al., Angew. Chem. Int. Ed. Engl.2009, 48, 9658–9662; Rohrbacher, F. et al., Helv. Chim. Acta.2018, 101; Baalmaan, et al, “A Bioorthogonal Click Chemistry Toolbox for Targeted Synthesis of Branched and Well-Defined Protein–Protein Conjugates”, Angew. Chem. Int. Ed.2020 (59): 12885-12893; Lang, et al, “Biorthogonal Reactions for Labeling Proteins”, J. Am. Chem. Soc, 2014, 9(1):16-20; Nair, et al., “The Thiol-Michael Addition Click Reaction: A Powerful and Widely Used Tool in Materials Chemistry”, Chem. Mater.201326(1):724-744; Kalia and Raines, “Hydrolytic Stability of Hydrazones and Oximes”, Angew. Chem. Int. Ed., 2008, 47:7523-7526. Examples of 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 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, the linker comprises a polyethylene glycol (PEG) moiety. In certain embodiments, the linker comprises a PEG of 1-1000 ethylene glycol units, wherein each unit is . In certain embodiments, the linker comprises 1-10 ethylene glycol units. In certain embodiments, linkers comprise 1-10 linker-nucleosides. In certain embodiments, linkers comprise 2-5 linker-nucleosides. In certain embodiments, linkers comprise exactly 3 linker-nucleosides. In certain embodiments, linkers comprise the TCA motif. 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-methyl cytosine, 4-N-benzoyl-5-methyl cytosine, adenine, 6-N- benzoyladenine, guanine and 2-N-isobutyrylguanine. It is typically desirable for linker-nucleosides to be cleaved from the oligonucleotide after it reaches a target tissue. Accordingly, linker-nucleosides are typically linked to one another and to the remainder of the oligonucleotide through cleavable bonds. In certain embodiments, such cleavable bonds are phosphodiester bonds. A linker may comprise a cleavable moiety. 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 moiety is selected from among: an amide, an ester, an ether, a phosphodiester, a phosphate ester, a carbamate, or a disulfide. In certain embodiments, a cleavable bond is a phosphodiester. In certain embodiments, a cleavable moiety comprises a phosphate or phosphodiester. In certain embodiments, the cleavable moiety is a phosphodiester linkage between an oligonucleotide and another chemical moiety attached at the 3’ or 5’ end of the oligonucleotide. In certain embodiments, delivery complexes disclosed herein comprise an oligonucleotide linked to an Fc domain by a linker, wherein the delivery complex is prepared using Click chemistry known in the art. Compounds have been prepared using Click chemistry wherein alkynyl phosphonate internucleoside linkages on an oligonucleotide attached to a solid support are converted into the 1,2,3-triazolylphosphonate internucleoside linkages and then cleaved from the solid support (Krishna et al., J. Am. Chem. Soc.2012, 134(28), 11618-11631), which is incorporated by reference herein in its entirety. Additional linkers suitable for use in several embodiments can be prepared by Click chemistry described in “Click Chemistry for Biotechnology and Materials Science” Ed. Joerg Laham, Wiley 2009, which is incorporated by reference herein in its entirety. In certain embodiment, the click reagent includes a bicyclo[6.1.0]nonyne (BCN) moiety having this structure: . reaction can be used to link a VHH domain or Fc polypeptide and an oligonucleotide by reacting: with an amine, including but not limited to the following compound: , to yield: , which ptide having an azide to yield: , wherein or Fc polypeptide, and wherein X or In certain embodiments, the VHH domain or Fc polypeptide comprises a polypeptide. In certain embodiments, the azido group is attached to an amino- acid side chain of the polypeptide. In certain embodiments, the azido group is attached to the N-terminus of the polypeptide. In certain embodiments, the azido group replaces the amino group of a lysine of the polypeptide. In certain embodiments, the azido group is introduced through a glutamine side chain using the enzyme microbial transglutaminase, as described in Strop, Bioconjugate Chemistry, (25):855-862, 2014, and the compound 11-Azido-3,6,9-trioxaundecan-1-amine, to yield a free azide as shown below: . an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the linker is prepared from the following compound: . complex comprises an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the linker comprises: . a delivery complex comprises an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the linker comprises: . comprises an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the complex comprises: ; wherein azido group of the VHH domain or Fc polypeptide; X represents the or polypeptide; and Y represents a portion of the oligomeric agent comprising the oligonucleotide. In certain embodiments, the VHH domain or Fc polypeptide comprises a polypeptide. In certain embodiments, the azido group is attached to an amino-acid side chain of the polypeptide. In certain embodiments, the azido group is attached to the N-terminus of the polypeptide. In certain embodiments, the azido group replaces the amino group of a lysine of the polypeptide. In certain embodiments, the azido group is introduced through a glutamine side chain using the enzyme microbial transglutaminase, as described in Strop, Bioconjugate Chemistry, (25):855-862, 2014, and the compound 11- Azido-3,6,9-trioxaundecan-1-amine, to yield a free azide as shown below: . an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker , wherein the delivery complex comprises: ; VHH domain or Fc polypeptide; X represents the remainder of the VHH domain or Fc polypeptide; and Y represents the remainder of the oligonucleotide. In certain embodiments, the VHH domain or Fc polypeptide comprises a polypeptide. In certain embodiments, the azido group is attached to an amino-acid side chain of the polypeptide. In certain embodiments, the azido group is attached to the N-terminus of the polypeptide. In certain embodiments, the azido group replaces the amino group of a lysine of the polypeptide. In certain embodiments, the azido group is introduced through a glutamine side chain using the enzyme microbial transglutaminase, as described in Strop, Bioconjugate Chemistry, (25):855-862, 2014, and the compound 11-Azido-3,6,9-trioxaundecan-1-amine, to yield a free azide as shown below: . oligonucleotide linked to a VHH domain or Fc a ; VHH domain or Fc polypeptide; X represents the Y represents the remainder of the oligonucleotide. In certain embodiments, the VHH domain or Fc polypeptide comprises a polypeptide. In certain embodiments, the azido group is attached to an amino-acid side chain of the polypeptide. In certain embodiments, the azido group is attached to the N-terminus of the polypeptide. In certain embodiments, the azido group replaces the amino group of a lysine of the polypeptide. In certain embodiments, the azido group is introduced through a glutamine side chain using the enzyme microbial transglutaminase, as described in Strop, Bioconjugate Chemistry, (25):855-862, 2014, and the compound 11-Azido-3,6,9-trioxaundecan-1-amine, to yield a free azide as shown below: . In certain embodiments, a Click reaction can be used to link a VHH domain or Fc polypeptide and an oligonucleotide by reacting: solution together with an including but not limited to the following compound: , to yield: , which peptide having an azide to yield: , domain or Fc polypeptide, and wherein X or In certain embodiments, the VHH domain or Fc polypeptide comprises a polypeptide. In certain embodiments, the azido group is attached to an amino- acid side chain of the polypeptide. In certain embodiments, the azido group is attached to the N-terminus of the polypeptide. In certain embodiments, the azido group replaces the amino group of a lysine of the polypeptide. In certain embodiments, the azido group is introduced through a glutamine side chain using the enzyme microbial transglutaminase, as described in Strop, Bioconjugate Chemistry, (25):855-862, 2014, and the compound 11-Azido-3,6,9-trioxaundecan-1-amine, to yield a free azide as shown below: . an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the linker is prepared from the following compound: . In certain embodiments, a delivery complex comprises an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the linker comprises: . a delivery complex comprises an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the linker comprises: . y complex comprises an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the compound comprises: ; an azido group of the VHH domain or Fc polypeptide; X represents the or Fc polypeptide; and Y represents a portion of the oligomeric agent comprising the oligonucleotide. In certain embodiments, the VHH domain or Fc polypeptide comprises a polypeptide. In certain embodiments, the azido group is attached to an amino-acid side chain of the polypeptide. In certain embodiments, the azido group is attached to the N-terminus of the polypeptide. In certain embodiments, the azido group replaces the amino group of a lysine of the polypeptide. In certain embodiments, the azido group is introduced through a glutamine side chain using the enzyme microbial transglutaminase, as described in Strop, Bioconjugate Chemistry, (25):855-862, 2014, and the compound 11- Azido-3,6,9-trioxaundecan-1-amine, to yield a free azide as shown below: . an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the delivery complex comprises: ; of the VHH domain or Fc polypeptide; X represents the remainder of the VHH domain or Fc polypeptide; and Y represents the remainder of the oligonucleotide. In certain embodiments, the VHH domain or Fc polypeptide comprises a polypeptide. In certain embodiments, the azido group is attached to an amino-acid side chain of the polypeptide. In certain embodiments, the azido group is attached to the N-terminus of the polypeptide. In certain embodiments, the azido group replaces the amino group of a lysine of the polypeptide. In certain embodiments, the azido group is introduced through a glutamine side chain using the enzyme microbial transglutaminase, as described in Strop, Bioconjugate Chemistry, (25):855-862, 2014, and the compound 11-Azido-3,6,9-trioxaundecan-1-amine, to yield a free azide as shown below: . an oligonucleotide linked to a VHH domain or a comprises: XN NN; of the VHH domain or Fc polypeptide; X represents the or and Y represents the remainder of the oligonucleotide. In certain embodiments, the VHH domain or Fc polypeptide comprises a polypeptide. In certain embodiments, the azido group is attached to an amino-acid side chain of the polypeptide. In certain embodiments, the azido group is attached to the N-terminus of the polypeptide. In certain embodiments, the azido group replaces the amino group of a lysine of the polypeptide. In certain embodiments, the azido group is introduced through a glutamine side chain using the enzyme microbial transglutaminase, as described in Strop, Bioconjugate Chemistry, (25):855-862, 2014, and the compound 11-Azido-3,6,9-trioxaundecan-1- amine, to yield a free azide as shown below: . an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the delivery complex comprises: , domain or Fc polypeptide; and Y comprises the oligonucleotide. In certain embodiments, a delivery complex comprises an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the delivery complex comprises: , igonucleotide; and Y comprises the VHH domain or Fc polypeptide. n cer a n em o ments, the linker comprises: Fc polypeptide; Y comprises the oligonucleotide, each Z is 4 , or n is 1 to 10. In certain embodiments, a delivery complex comprises an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the linker comprises: . a delivery complex comprises an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the linker comprises: . comprises an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the linker comprises: . a delivery complex comprises an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the linker comprises: . In certain embodiments, a delivery complex comprises an oligonucleotide linked to a VHH domain or Fc polypeptide by a linker, wherein the linker comprises: . preparation of the above starting materials and intermediates can be found in one or more Agard, et al., “A Strain-Promoted [3 + 2] Azide-Alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems.” J. Am. Chem. Soc.2004, 126:15046– 15047; Lang, et al, “Biorthogonal Reactions for Labeling Proteins”, J. Am. Chem. Soc, 2014, 9(1):16-20; Nair, et al., “The Thiol-Michael Addition Click Reaction: A Powerful and Widely Used Tool in Materials Chemistry”, Chem. Mater.201326(1):724-744; WO2011 / 136645; Kömel and Kool, “Oximes and Hydrazones in Bioconjugation: Mechanism and Catalysis, Chem. Rev., 2017, 117:10358-10376; Wang, et al., “Polyfluorophenyl Ester-Terminated Homobifunctional CrossLinkers for Protein Conjugation”, Synlett, 2017, 28: 1934-1938; Kishimoto, et al, “Site-Specific Chemical Conjugation of Antibodies by Using Affinity Peptide for the Development of Therapeutic Antibody Format”, Bioconj. Chem., 2019, 30:698-702. Certain Oligonucleotides provided herein are delivery complexes comprising oligomeric agents which consist of linked nucleosides. Oligonucleotides may be unmodified oligonucleotides or may be modified oligonucleotides. Modified oligonucleotides comprise at least one modification relative to unmodified nucleic acids. 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 Modified nucleosides comprise a modified sugar moiety or a modified nucleobase or both a modifed sugar moiety and a modified nucleobase. Certain Sugar Moieties Modified sugar moieties include modified furanosyl sugar moieties, cyclic sugar surrogates, acyclic sugar surrogates, and sugar mimics. In certain embodiments, modified sugar moieties are non-bicyclic modified furanosyl sugar moieties. In certain embodiments, modified sugar moieties are bicyclic or tricyclic furanosyl sugar moieties. In certain embodiments, modified sugar moieties are sugar surrogates. 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 substituent groups including, but not limited to, substituents at the 2’, 3’, 4’, and / or 5’ positions, as numbered based on ribose: embodiments, non-bicyclic modified sugar moieties are 2’-substituted sugar moieties and 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 among: 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 among: 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 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), 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) Mal Cane 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, selected from cyclic sugar surrogates and acyclic sugar surrogates. A cyclic sugar surrogate can be represented by Formula Ia: Wherein: J is H, C1-C6alkyl, or C2-C6alkenyl; X is O, S, C(R1R2), N(R3), C(R1)=C(R2), C(R1R2)-C(R1R2), O-C(R1R2), C(R1R2)-O, S-C(R1R2), C(R1R2)-S, N(R3)-C(R1R2), or C(R1R2)-N(R3); Y is C(R1R2), C(R1)=C(R2), or C(R1R2)-C(R1R2); Z is C(G1G2), C(G1)=C(R1), C(R1)=C(G1), C(G1G2)-C(R1R2), C(R1R2)-C(G1G2), C(G1G2)-C(R1R2)- C(R1R2), or C(R1R2)-C(R1R2)-C(G1G2); Q is CH or N; each R1and R2is independently H, OH, C1-C6alkyl, or N(R4); wherein if R1is OH, then R2is not OH; each R3and R4is independently H, C1-C6alkyl, or C(=O)R5, wherein R5is C1-C6alkyl; each G1and G2is independently H, OH, halogen or O-[C(R6)(R7)]q-[(C=O)s-XG]j-R8; wherein if G1is OH, then G2is not OH; each R6and R7is, independently, H, halogen, C1-C6alkyl or substituted C1-C6alkyl; each XGis O, S or N(E1); R8is H, halogen, C1-C6alkyl, substituted C1-C6alkyl, C2-C6alkenyl, substituted C2-C6alkenyl, C2-C6alkynyl, substituted C2-C6alkynyl or N(E2)(E3); E1, E2and E3are each, independently, H, C1-C6alkyl or substituted C1-C6alkyl; m is 0 or 1; p is 0 or 1; q is from 1 to 6; s is 0 or 1; j is 0 or 1; and with the proviso that if X is O, Z is C(G1G2), and Q is CH, then m is 1. In certain such embodiments, the oxygen atom of the sugar moiety is replaced, e.g., with a sulfur, carbon or nitrogen atom (X is S, C(R1R2), or N(R3)). 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”), where X is O- C(R1R2), p is 1, Z is C(G1G2), and m is 0. Such tetrahydropyrans may be further modified or substituted. Nucleosides comprising such modified tetrahydropyrans include but are not limited to hexitol nucleic acid (“HNA”), altritol nucleic acid (G1=OH; G2=H; “ANA”), and fluoro HNA: (G1=F; see e.g.., Egli, et. al., J Am Chem Soc (2011) 133(41):16642-16649, Swayze et al., U.S.8,088,904; and Swayze et al., U.S.8,440,803); FHNA can also be referred to as a F-THP or 3'-fluoro tetrahydropyran or 3'-FHNA). 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 Formula Ia, wherein X is O, Y and Z are each CH2, and Q is N. In certain embodiments, a morpholino is 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 are acyclic sugar surrogates and have Formula IIa or IIIa: Wherein: X is O, S, C(R4R5), N(E1), N(E1)-C(=O); each J1and J2is independently H or C1-C6alkyl; n is 0, 1 or 2; m is 0, 1, or 2; o is 0 or 1; s is 0 or 1; R1is H, OH, halogen, C1-C6alkyl, C1-C6alkoxy, C2-C6alkenyl, C2-C6alkynyl, or (CH2)qR7R2and R3are each independently H, OH, halogen, C1-C6alkyl, C1-C6alkoxy, C2-C6alkenyl, C2-C6alkynyl, S-CH3, N(CH3)(CH3), OCH2CH2OCH3, O-alkylamino, or (CH2)qR7; E1is H, C1-C6alkyl or substituted C1-C6alkyl; R4and R5are independently H, OH, C1-C6alkyl, or N(R6); wherein if R4is OH, then R5is not OH; R6is H, C1-C6alkyl, or C(=O)R8, wherein R8is C1-C6alkyl; R7is OH, halogen, methoxy, ethoxy, azido, and C2-C6alkenyl, or C2-C6alkynyl, and q is 1, 2, or 3. In certain embodiments, acyclic sugar surrogates are the “unlocked” sugar structure of UNA (unlocked nucleic acid) nucleosides. Representative U.S. publications that teach the preparation of UNA include, but are not limited to, U.S. Patent Publication No.2011 / 0313020. In certain embodiments, acyclic sugar surrogates are the glycerol as found in GNA (glycol nucleic acid) nucleosides, having formula IIa wherein n is 1, m and o are 0, s is 1, and J2, R2, and R3are each H, or the butyl as found in acyclic butyl nucleic acid, having formula IIa wherein n is 2, m and o are 0, s is 1, and J2, R2, and R3are each H. In certain embodiments, acyclic sugar surrogates are also known as “C3 spacers” and have formula IIa wherein n and o are 1; m and s are 0, and J1, J2, R1, and R3are each H. Further acyclic sugar surrogates include those described in Manoharan et al., U.S.10,913,767; US patent publication US2021 / 0238595; and PCT publication WO2023 / 109940. In certain embodiments, modified oligonucleotides include one or more sugar mimic, in which a group of atoms other than a “furanosyl sugar moiety” or a “sugar surrogate” form the portion of a nucleoside corresponding to the β-D-ribosyl sugar in RNA. In certain embodiments, a sugar mimic is a portion of the backbone of a peptide nucleic acid, while the remainder of the backbone of the peptide nucleic acid is an internucleoside linkage. 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. 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): wherein: R2Ais H, C1-C6alkyl, substituted C1-C6alkyl, C1-C6thioalkyl, or substituted C1-C6thioalkyl, C1-C6alkyloxy, or substituted C1-C6alkyloxy; R6Ais H, N(Ra)(Rb), oxo, 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): III selected 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): 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), N1-methyl 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. 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 is any of those described in WO2021 / 030778, incorporated by reference herein. In certain embodiments, a modified internucleoside linkage comprises the formula: wherein indepe ch such internucleoside linking group of a modified oligonucleotide: X is selec e rom 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 linker; R3is selected from an aryl, a substituted aryl, CH3, N(CH3)2, OCH3and a linker; R4is selected from OCH3, OH, C1-C6alkyl, substituted C1-C6alkyl and a linker; 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 having a formula: In certain internucleoside linkage may comprise a chiral center. In certain embodiments, modified oligonucleotides comprising (Rp) and / or (Sp) mesyl phosphoramidates comprise one or more of the following formulas, respectively, wherein “B” indicates a nucleobase: . 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. 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:

[0002] ing 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 linker) may be attached to the inverted nucleoside. Such terminal inverted nucleosides can be attached to either or both ends of an oligonucleotide. 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. 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). 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. RNAse H Agents In certain embodiments, modified oligonucleotides comprise a deoxy region. In certain embodiments, each nucleoside of the deoxy region comprises a 2’-β-D-deoxyribosyl sugar moiety. 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, exactly one nucleoside within the deoxy region comprises a modified sugar moiety, and the remainder of the nucleosides comprise 2’-β-D-deoxyribosyl sugar moieties. In certain embodiments, the modified sugar moiety is a 2’-OMe 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, the 5’-region and the 3’-region each comprise a modified sugar moiety. In certain embodiments, the deoxy region is 10 nucleosides, with each nucleoside comprising a 2’-β-D- deoxyribosyl sugar moiety. In certain embodiments, such modified oligonucleotides are referred to as “gapmers”. In certain such embodiments, the 5’-region and the 3’-region each comprise exactly three bicyclic nucleosides (A “3-10-3 BNA gapmer”). In certain embodiments, each BNA is a cEt (a “3-10-3 cEt gapmer”, or each BNA is an LNA (a “3-10-3 LNA gapmer”). In certain alternative embodiments, the 5’- region and the 3’-region each comprise exactly five MOE nucleosides (A “5-10-5 MOE gapmer”). In certain embodiments, modified oligonucleotides comprise or consist of a region having a fully modified sugar motif. In such embodiments, each nucleoside of the fully modified region 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 region having a fully modified sugar motif, wherein each nucleoside within the fully modified region 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 comprises the same 2’-modification. 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-methyl cytosines. In certain embodiments, all of the cytosine nucleobases are 5-methyl cytosines 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’-deoxyribosyl moiety. In certain embodiments, the modified nucleobase is selected from: a 2-thiopyrimidine and a 5-propynylpyrimidine. 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 (P=O). In certain embodiments, each internucleoside linking group of a modified oligonucleotide is a phosphorothioate internucleoside linkage (P=S). 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 such 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, Rp motif. In certain embodiments, populations of modified oligonucleotides are enriched for modified oligonucleotides comprising such internucleoside linkage motifs. 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 Certain Modified Oligonucleotides In certain 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. Certain Populations of Modified Oligonucleotides Populations of modified oligonucleotides in which all of the modified oligonucleotides of the population have the same molecular formula can be stereorandom populations or chirally enriched populations. All of the chiral centers of all of the modified oligonucleotides are stereorandom in a stereorandom population. In a chirally enriched population, at least one particular chiral center is not stereorandom in the modified oligonucleotides of the population. In certain embodiments, the modified oligonucleotides of a chirally enriched population are enriched for β-D ribosyl sugar moieties, and all of the phosphorothioate internucleoside linkages are stereorandom. In certain embodiments, the modified oligonucleotides of a chirally enriched population are enriched for both β-D ribosyl sugar moieties and at least one, particular phosphorothioate internucleoside linkage in a particular stereochemical configuration. Nucleobase Sequence In certain embodiments, oligonucleotides (unmodified or modified oligonucleotides) are further described by their nucleobase sequence. In certain embodiments oligonucleotides have a nucleobase sequence that is complementary to a second oligonucleotide or an identified reference nucleic acid, such as a target nucleic acid. In certain such embodiments, a region of an oligonucleotide has a nucleobase sequence that is complementary to a second oligonucleotide or an identified reference nucleic acid, 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 nucleic acid, such as a target nucleic acid. Oligomeric Duplexes In certain embodiments, oligomeric agents described herein comprise an oligonucleotide, having a nucleobase sequence complementary to that of a target nucleic acid. In certain embodiments, an oligonucleotide is paired with a second oligonucleotide to form an oligomeric duplex. Such oligomeric duplexes comprise a first oligonucleotide having a region complementary to a target nucleic acid and a second oligonucleotide having a region complementary to the first oligonucleotide. In certain embodiments, the first oligonucleotide of an oligomeric duplex comprises or consists essentially of a modified or unmodified oligonucleotide and a linker and / or a terminal group. In certain embodiments, the first oligonucleotide of an oligomeric duplex comprises or consists essentially of a modified or unmodified oligonucleotide. In certain embodiments, the second oligonucleotide of an oligomeric duplex comprises or consists essentially of a modified or unmodified oligonucleotide and a linker and / or a terminal group. Either or both oligonucleotide of an oligomeric duplex may comprise a linker and / or a terminal group. In certain embodiments, the oligonucleotide is directly connected to the linker and the linker is directly connected to a VHH domain or Fc polypeptide. Each oligonucleotide of an oligomeric duplex may include non- complementary overhanging nucleosides. In certain embodiments, an overhanging nucleoside may be complementary to the target nucleic acid. In certain embodiments, an overhanging nucleoside is not complementary to a target nucleic acid. In certain embodiments, the two oligonucleotides have at least one mismatch relative to one another. In certain embodiments, the oligomeric duplex is an antisense agent. In certain embodiments, the first oligonucleotide is a modified oligonucleotide. In certain embodiments, the first modified oligonucleotide is an antisense oligonucleotide. In certain embodiments, the second oligonucleotide is a modified oligonucleotide. In certain embodiments, the second modified oligonucleotide is a sense oligonucleotide. In certain embodiments, the first modified oligonucleotide is an antisense RNAi oligonucleotide. In certain embodiments, the second modified oligonucleotide is a sense RNAi oligonucleotide. In certain embodiments, the nucleobase sequence of the second modified oligonucleotide comprises a complementary region of 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, at least 20, or 21 nucleobases that is at least 90% complementary to the nucleobase sequence of an equal portion of the first modified oligonucleotide. In certain embodiments, the nucleobase sequence of the second modified oligonucleotide comprises a complementary region of 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, at least 20, or 21 nucleobases that is at least 95% complementary to the nucleobase sequence of an equal portion of the first modified oligonucleotide. In certain embodiments, the nucleobase sequence of the second modified oligonucleotide comprises a complementary region of 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, at least 20, or 21 nucleobases that is 100% complementary to the nucleobase sequence of an equal portion of the first modified oligonucleotide. In certain embodiments, the oligomeric duplex is an antisense agent. In certain embodiments, the first modified oligonucleotide is an antisense RNAi oligonucleotide having a length of 21-23 oligonucleotides. In certain embodiments, the second modified oligonucleotide is a sense RNAi oligonucleotide having a length of 19-21 oligonucleotides. In any of the oligomeric duplexes described herein, at least one nucleoside of the first modified oligonucleotide and / or the second modified oligonucleotide can comprise a modified sugar moiety. Examples of suitable modified sugar moieties include, but are not limited to, a bicyclic sugar moiety, such as a 2’-4’ bridge selected from –O-CH2-; and –O-CH(CH3)-, and a non-bicyclic sugar moiety, such as a 2’-MOE sugar moiety, a 2’-F sugar moiety, a 2’-OMe sugar moiety, or a 2’-NMA sugar moiety. In certain embodiments, at least one nucleoside of the first modified oligonucleotide and / or the second modified oligonucleotide can comprise an unmodified 2’-deoxyribosyl sugar moiety. In certain embodiments, at least 80%, at least 90%, or 100% of the nucleosides of the first modified oligonucleotide and / or the second modified oligonucleotide comprises a modified sugar moiety selected from 2’-F and 2’-OMe. In certain embodiments, one or more 2’- F sugar moieties have a conformation other than 2’-β-D-ribosyl. In certain embodiments, one or more 2’-F sugar moieties is in the 2’-β-D-xylosyl conformation. In any of the oligomeric duplexes described herein, at least one nucleoside of the first modified oligonucleotide and / or the second modified oligonucleotide can comprise a sugar surrogate. Examples of suitable sugar surrogates include, but are not limited to, morpholino, hexitol nucleic acid (HNA), fluoro- hexitol nucleic acid (F-HNA), the sugar surrogates of glycol nucleic acid (GNA) and unlocked nucleic acid (UNA). In certain embodiments, at least one nucleoside of the first modified oligonucleotide comprises a sugar surrogate, which can be a GNA. In any of the oligomeric duplexes described herein, at least one internucleoside linkage of the first modified oligonucleotide and / or the second modified oligonucleotide can comprise a modified internucleoside linkage. In certain embodiments, the modified internucleoside linkage is a phosphorothioate internucleoside linkage. In certain embodiments, at least one of the first, second, or third internucleoside linkages from the 5’ end and / or the 3’ end of the first modified oligonucleotide comprises a phosphorothioate linkage. In certain embodiments, at least one of the first, second, or third internucleoside linkages from the 5’ end and / or the 3’ end of the second modified oligonucleotide comprises a phosphorothioate linkage. In certain embodiments, the modified internucleoside linkage is a mesyl phosphoramidate internucleoside linkage. In certain embodiments, at least one of the first or second internucleoside linkages from the 5’ end and / or the 3’ end of the first modified oligonucleotide comprises a mesyl phosphoramidate internucleoside linkage. In certain embodiments, at least one of the first or second internucleoside linkages from the 5’ end and / or the 3’ end of the second modified oligonucleotide comprises a mesyl phosphoramidate internucleoside linkage. In any of the oligomeric duplexes described herein, at least one internucleoside linkage of the first modified oligonucleotide and / or the second modified oligonucleotide can comprise a phosphodiester internucleoside linkage. In any of the oligomeric duplexes described herein, each internucleoside linkage of the first modified oligonucleotide and / or the second modified oligonucleotide can be independently selected from a phosphodiester, a phosphorothioate, or a mesyl phosphoramidate internucleoside linkage. In any of the oligomeric duplexes described herein, each internucleoside linkage of the first modified oligonucleotide and / or the second modified oligonucleotide can be independently selected from a phosphodiester or a phosphorothioate internucleoside linkage. In any of the oligomeric duplexes described herein, each internucleoside linkage of the first modified oligonucleotide and / or the second modified oligonucleotide can be independently selected from a phosphodiester or a mesyl phosphoramidate internucleoside linkage. In any of the oligomeric duplexes described herein, the internucleoside linkage motif of the first modified oligonucleotide can be ssooooooooooooooooooss, wherein each “s” is a phosphorothioate internucleoside linkage and each “o” is a phosphodiester internucleoside linkage. In any of the oligomeric duplexes described herein, the internucleoside linkage motif of the second modified oligonucleotide can be ssooooooooooooooooss, wherein each “s” is a phosphorothioate internucleoside linkage and each “o” is a phosphodiester internucleoside linkage. In any of the oligomeric duplexes described herein, at least one nucleobase of the first modified oligonucleotide and / or the second modified oligonucleotide can be modified nucleobase. In certain embodiments, the modified nucleobase is 5-methylcytosine. In any of the oligomeric duplexes described herein, the first modified oligonucleotide can comprise a stabilized phosphate group attached to the 5’ position of the 5’-most nucleoside. In certain embodiments, the stabilized phosphate group comprises a cyclopropyl phosphonate or an (E)-vinyl phosphonate. In some embodiments, the oligomeric duplex has a motif as described in International Publication No. WO 2022 / 174053. In any of the oligomeric duplexes described herein, the first oligonucleotide and / or the second oligonucleotide can comprise a linker connected to a VHH domain, Fc polypeptide, or other molecule. In certain embodiments, an oligomeric agent comprises exactly one linker. In certain embodiments, an oligomeric agent comprises exactly two linkers. In certain embodiments, an oligomeric agent comprises 0, 1, 2, 3, or 4 linkers. In alternative embodiments, an oligomeric agent comprises two linkers attached at distinct parts of a single modified oligonucleotide, wherein one linker connects to a Fc polypeptide, and the second linker connects to a VHH domain. In certain embodiments, a linker is attached to the first modified oligonucleotide at the 5’-end of the first modified oligonucleotide. In certain embodiments, a linker is attached to the first modified oligonucleotide at the 3’-end of the first modified oligonucleotide. In certain embodiments, a linker is attached to the first modified oligonucleotide at an internal position. In certain embodiments, a linker is attached to the first modified oligonucleotide through a 2’-modification of a furanosyl sugar moiety. In certain embodiments, a linker is attached to the first modified oligonucleotide through a modified internucleoside linkage. In certain embodiments, a linker is attached to the second modified oligonucleotide at the 5’-end of the modified oligonucleotide. In certain embodiments, a linker is attached to the second modified oligonucleotide at the 3’-end of the modified oligonucleotide. In certain embodiments, a linker is attached to the second modified oligonucleotide at an internal position. In certain embodiments, a linker is attached to the second modified oligonucleotide through a 2’-modification of a furanosyl sugar moiety. In certain embodiments, a linker is attached to the second modified oligonucleotide through a modified internucleoside linkage. In certain embodiments, the linker connects to a VHH domain. In certain embodiments, the VHH domain is a transferrin receptor binding VHH domain. In certain embodiments, the linker connects to an Fc polypeptide. In certain embodiments, the first modified oligonucleotide is connected to a linker that connects to an Fc polypeptide, and the second modified oligonucleotide is connected to a linker that connects to a transferrin receptor binding VHH domain. In certain embodiments, the first modified oligonucleotide is connected to a linker that connects to a transferrin receptor binding VHH domain, and the second modified oligonucleotide is connected to a linker that connects to a Fc polypeptide. Antisense Activity In certain embodiments, oligomeric agents comprise antisense oligonucleotides that are capable of hybridizing to a target nucleic acid, resulting in at least one antisense activity; such oligomeric agents are antisense agents. In certain embodiments, antisense agents have antisense activity when they reduce or inhibit the amount or activity of a target nucleic acid by 25% or more in the standard cell assay. In certain embodiments, antisense agents selectively affect one or more target nucleic acid. Such antisense agents 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 oligonucleotide to a target nucleic acid results in recruitment of a protein that cleaves the target nucleic acid. For example, certain antisense agents (“RNAse H agents”) 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, antisense oligonucleotides described herein are sufficiently “DNA-like” to elicit RNase H activity. In certain embodiments, one or more non-DNA-like nucleoside in the deoxy region is tolerated. In certain antisense activities, an antisense agent or a portion of an antisense agent is loaded into an RNA-induced silencing complex (RISC), ultimately resulting in cleavage of the target nucleic acid. For example, certain antisense agents result in cleavage of the target nucleic acid by Argonaute. Antisense agents comprising antisense oligonucleotides that are loaded into RISC are RNAi agents. RNAi agents may be double-stranded (siRNA) or single-stranded (ssRNA). In certain embodiments, hybridization of an antisense oligonucleotide 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 oligonucleotide to the target nucleic acid results in alteration of splicing of the target nucleic acid. In certain embodiments, hybridization of an antisense oligonucleotide 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 oligonucleotide 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. Certain Target Nucleic Acids In certain embodiments, oligomeric agents comprise or consist 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 such 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 such embodiments, the target non-coding RNA is selected from: a long non- coding RNA, a short non-coding RNA, an intronic RNA molecule. Complementarity / Mismatches to the Target Nucleic Acid 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 a 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 are complementary to the target nucleic acid over the entire length of the oligonucleotide. In certain embodiments, oligonucleotides are 99%, 95%, 90%, 85%, or 80% 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. 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, the 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. In certain embodiments, the mismatch is at position 1, 2, 3, or 4 from the 5’-end of the wing region. In certain embodiments, the mismatch is at position 4, 3, 2, or 1 from the 3’-end of the wing region. Certain Methods In certain embodiments, polypeptides described herein (e.g., Fc polypeptides, antibodies and binding fragments, transferrin receptor VHH domains) are produced using any method known in the art to be useful for the synthesis of polypeptides (e.g., antibodies), in particular, by chemical synthesis or by recombinant expression, and are preferably produced by recombinant expression techniques. In some instances, an antibody or antigen binding fragment thereof is expressed recombinantly, and the nucleic acid encoding the antibody or its binding fragment is assembled from chemically synthesized oligonucleotides (e.g., as described in Kutmeier et al., 1994, BioTechniques 17:242), which involves the synthesis of overlapping oligonucleotides containing portions of the sequence encoding the antibody, annealing and ligation of those oligonucleotides, and then amplification of the ligated oligonucleotides by PCR. Alternatively, a nucleic acid molecule encoding an antibody is optionally generated from a suitable source (e.g., an antibody cDNA library, or cDNA library generated from any tissue or cells expressing the immunoglobulin) by PCR amplification using synthetic primers hybridizable to the 3' and 5' ends of the sequence or by cloning using an oligonucleotide probe specific for the particular gene sequence. In some instances, an antibody or antigen binding fragment is optionally generated by immunizing an animal, such as a rabbit, to generate polyclonal antibodies or, more preferably, by generating monoclonal antibodies, e.g, as described by Kohler and Milstein (1975, Nature 256:495-497) or, as described by Kozbor et al. (1983, Immunology Today 4:72) or Cole et al. (1985 in Monoclonal Antibodies and Cancer Therapy , Alan R. Liss, Inc., pp.77-96). Alternatively, a clone encoding at least the Fab portion of the antibody is optionally obtained by screening Fab expression libraries ( e.g. , as described in Huse et al., 1989, Science 246:1275- 1281) for clones of Fab fragments that bind the specific antigen or by screening antibody libraries (See, e.g., Clackson et al., 1991, Nature 352:624; Hane et al., 1997 Proc. Natl. Acad. Sci. USA 94:4937). In some embodiments, techniques developed for the production of “chimeric antibodies” (Morrison et al., 1984, Proc. Natl. Acad. Sci.81:851-855; Neuberger et al., 1984, Nature 312:604-608; Takeda et al., 1985, Nature 314:452-454) by splicing genes from a mouse antibody molecule of appropriate antigen specificity together with genes from a human antibody molecule of appropriate biological activity are used. A chimeric antibody is a molecule in which different portions are derived from different animal species, such as those having a variable region derived from a murine monoclonal antibody and a human immunoglobulin constant region, e.g, humanized antibodies. In some embodiments, techniques described for the production of single chain antibodies (U.S. Pat. No.4,694,778; Bird, 1988, Science 242:423-42; Huston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879- 5883; and Ward et al., 1989, Nature 334:544-54) are adapted to produce single chain antibodies. Single chain antibodies are formed by linking the heavy and light chain fragments of the Fv region via an amino acid bridge, resulting in a single chain polypeptide. Techniques for the assembly of functional Fv fragments in E. coli are also optionally used (Skerra et al., 1988, Science 242:1038-1041). In some embodiments, an expression vector comprising the nucleotide sequence of an antibody or the nucleotide sequence of an antibody is transferred to a host cell by conventional techniques (e.g, electroporation, liposomal transfection, and / or calcium phosphate precipitation), and the transfected cells are then cultured by conventional techniques to produce the antibody. In specific embodiments, the expression of the antibody is regulated by a constitutive, an inducible or a tissue, specific promoter. In some embodiments, a variety of host-expression vector systems is utilized to express an antibody or its binding fragment described herein. Such host-expression systems represent vehicles by which the coding sequences of the antibody is produced and subsequently purified, but also represent cells that are, when transformed or transfected with the appropriate nucleotide coding sequences, express an antibody or its binding fragment in situ. These include, but are not limited to, microorganisms such as bacteria (e.g, E. coli and B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing an antibody or its binding fragment coding sequences; yeast (e.g ., Saccharomyces Pichia) transformed with recombinant yeast expression vectors containing an antibody or its binding fragment coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing an antibody or its binding fragment coding sequences; plant cell systems infected with recombinant virus expression vectors (e.g, cauliflower mosaic virus (CaMV) and tobacco mosaic virus (TMV)) or transformed with recombinant plasmid expression vectors (e.g, Ti plasmid) containing an antibody or its binding fragment coding sequences; or mammalian cell systems (e.g, COS, CHO, BH, 293, 293T, 3T3 cells) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g, metallothionein promoter) or from mammalian viruses (e.g. the adenovirus late promoter; the vaccinia virus 7.5K promoter). For long-term, high-yield production of recombinant proteins, stable expression is preferred. In some instances, cell lines that stably express an antibody are optionally engineered. Rather than using expression vectors that contain viral origins of replication, host cells are transformed with DNA controlled by appropriate expression control elements (e.g, promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Following the introduction of the foreign DNA, engineered cells are then allowed to grow for 1-2 days in an enriched media, and then are switched to a selective media. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci that in turn are cloned and expanded into cell lines. This method can advantageously be used to engineer cell lines which express the antibody or its binding fragments. In some instances, a number of selection systems are used, including but not limited to the herpes simplex virus thymidine kinase (Wigler et al, 1977, Cell 11:223), hypoxanthine- guanine phosphoribosyltransferase (Szybalska & Szybalski, 192, Proc. Natl. Acad. Sci. USA 48:202), and adenine phosphoribosyltransferase (Lowy et al., 1980, Cell 22:817) genes are employed in tk-, hgprt- or aprt- cells, respectively. Also, antimetabolite resistance are used as the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler et al, 1980, Proc. Natl. Acad. Sci. USA 77:357; O'Hare et ak, 1981, Proc. Natl. Acad. Sci. USA 78:1527); gpt, which confers resistance to mycophenolic acid (Mulligan & Berg, 1981, Proc. Natl. Acad. Sci. USA 78:2072); neo, which confers resistance to the aminoglycoside G- 418 (Clinical Pharmacy 12:488-505; Wu and Wu, 1991, Biotherapy 3:87-95; Tolstoshev, 1993, Ann. Rev. Pharmacol. Toxicol.32:573-596; Mulligan, 1993, Science 260:926-932; and Morgan and Anderson, 1993, Ann. Rev. Biochem.62:191-217; May, 1993, TIB TECH 11(5): 155-215) and hygro, which confers resistance to hygromycin (Santerre et ak, 1984, Gene 30:147). Methods commonly known in the art of recombinant DNA technology which can be used are described in Ausubel et al. (eds., 1993, Current Protocols in Molecular Biology, John Wiley & Sons, NY; Kriegler, 1990, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY; and in Chapters 12 and 13, Dracopoli et al. (eds), 1994, Current Protocols in Human Genetics, John Wiley & Sons, NY.; Colberre-Garapin et al., 1981, . / . Mol. Biol.150:1). In some instances, the expression levels of an antibody are increased by vector amplification (for a review, see Bebbington and Hentschel, The use of vectors based on gene amplification for the expression of cloned genes in mammalian cells in DNA cloning, Vol.3. (Academic Press, New York, 1987)). When a marker in the vector system expressing an antibody is amplifiable, an increase in the level of inhibitor present in culture of host cell will increase the number of copies of the marker gene. Since the amplified region is associated with the nucleotide sequence of the antibody, production of the antibody will also increase (Crouse et al., 1983, Mol. Cell Biol.3:257). In some instances, any method known in the art for purification or analysis of an antibody or antibody conjugates is used, for example, by chromatography ( e.g. , ion exchange, affinity, particularly by affinity for the specific antigen after Protein A, and sizing column chromatography), centrifugation, differential solubility, or by any other standard technique for the purification of proteins. Exemplary chromatography methods included, but are not limited to, strong anion exchange chromatography, hydrophobic interaction chromatography, size exclusion chromatography, and fast protein liquid chromatography. Certain target nucleic acids Modified oligonucleotides targeting muscle nucleic acids have been described previously that may be useful in conjunction with the provided invention, and in particular modified oligonucleotides may be comprised in compositions of the invention. In certain embodiments, a target nucleic acid is a central nervous system (CNS) target nucleic acid. In certain embodiments, the target nucleic acid is selected from APP, ASPA, ATXN1, ATXN2, ATXN3, CD20, CLN3, CLN7, DARS2, DMD, DMPK, GFAP, FUS, LRRK2, HTT, SMN2, SNCA, SOD1, TAU, TECPR2, TREM2, TTR, TUG1, and UBE3A. Certain Pharmaceutical Compositions In certain embodiments, a delivery complex provided herein is a formulated as a pharmaceutical composition. The pharmaceutical composition may contain one or more excipients to facilitate systemic delivery of the delivery complex, for example, by infusion or subcutaneous injection. In certain embodiments, a pharmaceutical composition is 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. 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. Under certain conditions, certain oligonucleotides and oligomeric agents disclosed herein act as acids. Although such compounds may be drawn or described in protonated (free acid) form, in ionized (anion) form, or ionized and in association with a cation (salt) form, aqueous solutions of such compounds exist in equilibrium among such forms. For example, a phosphate linkage of an oligonucleotide in aqueous solution exists in equilibrium among free acid, anion, and salt forms. Unless otherwise indicated, compounds described herein are intended to include all such forms. Moreover, certain oligonucleotides have several such linkages, each of which is in equilibrium. Thus, oligonucleotides in solution exist in an ensemble of forms at multiple positions all at equilibrium. The term “oligonucleotide” is intended to include all such forms. Drawn structures necessarily depict a single form. Nevertheless, unless otherwise indicated, such drawings are likewise intended to include corresponding forms. Herein, a structure depicting the free acid of a compound followed by the term “or salts thereof” expressly includes all such forms that may be fully or partially protonated / de-protonated / in association with a cation. In certain instances, one or more specific cation is identified. Nonlimiting disclosure and incorporation by reference Where permitted, each of the literature and patent publications listed herein is incorporated by reference in its entirety. While certain compounds, compositions and methods described herein have been described with specificity in accordance with certain embodiments, the following examples serve only to illustrate the compounds described herein and are not intended to limit the same. Each of the references, GenBank accession numbers, ENSEMBL identifiers, and the like recited in the present application is incorporated herein by reference in its entirety. The sequence listing accompanying this filing identifies each nucleic acid sequence as either “RNA” or “DNA” as required; however, one of skill in the art will readily appreciate that designation of “RNA” or “DNA” to describe modified oligonucleotides is, in certain instances, arbitrary. For example, an oligonucleotide comprising a nucleoside comprising a 2’-OH sugar moiety and a thymine base could be described as a DNA having a modified sugar (2’-OH in place of one 2’-H of DNA) or as an RNA having a modified base (thymine (5-methyl uracil)) in place of an uracil of RNA); and certain nucleic acid compounds described herein comprise one or more nucleosides comprising modified sugar moieties having 2’- substituent(s) that are neither OH nor H. One of skill in the art will readily appreciate that labeling such nucleic acid compounds “RNA” or “DNA” does not alter or limit the description of such nucleic acid compounds. Herein, the description of compounds as having “the nucleobase sequence of” a SEQ ID NO. describes only the nucleobase sequence. Accordingly, absent additional description, such description of compounds by reference to a nucleobase sequence of a SEQ ID NO. does not limit sugar or internucleoside linkage modifications or presence or absence of additional substituents such as a conjugate group. Further, absent additional description, the nucleobases of a compound “having the nucleobase sequence of” a SEQ ID NO. include such compounds having modified forms of the identified nucleobases as described herein. Herein, the description of compounds by chemical notation (subscripts and / or superscripts to indicate chemical modifications) without reference to a specific Compound No. include only each noted modification, but may include additional substituents, such as a conjugate group, unless otherwise indicated. For example, the chemical notation of “AesTkomCezGdsC” indicates a compound wherein the first nucleoside comprises a 2’- MOE sugar moiety (indicated by the “e” subscript) and an unmodified adenine nucleobase linked to the second nucleoside via a phosphorothioate linkage (indicated by the “s” subscript); the second nucleoside comprises a cEt sugar moiety (indicated by the “k” subscript) and an unmodified thymine nucleobase linked to the third nucleoside via a phosphodiester linkage (indicated by the “o” subscript); the third nucleoside comprises a 2’-MOE sugar moiety and a 5-methyl modified cytosine nucleobase (indicated by the “m” superscript) linked to the fourth nucleoside via a mesylphosphoramidate linkage (indicated by the “z” subscript); the fourth nucleoside comprises a 2’-β-D-deoxyribosyl sugar moiety (indicated by the “d” subscript) and an unmodified guanine nucleobase linked to the fifth nucleoside with a phosphorothioate linkage; and the fifth nucleoside comprises a 2’-β-D-deoxyribosyl sugar moiety and an unmodified cytosine nucleobase; and the compound may include additional substituents, such as a conjugate group. Herein, where a specific compound (e.g., with reference to a Compound No.) is described (as in the examples) by chemical notation, each nucleobase, sugar, and internucleoside linkage of such specific compound is modified only as indicated . Accordingly, in the context of a description of a specific compound having a particular Compound No., “AesTkomCezGdsC” indicates a compound wherein the first nucleoside comprises a 2’-MOE sugar moiety (indicated by the “e” subscript) and an unmodified adenine nucleobase linked to the second nucleoside via a phosphorothioate linkage (indicated by the “s” subscript); the second nucleoside comprises a cEt sugar moiety (indicated by the “k” subscript) and an unmodified thymine nucleobase linked to the third nucleoside via a phosphodiester linkage (indicated by the “o” subscript); the third nucleoside comprises a 2’-MOE sugar moiety and a 5-methyl modified cytosine nucleobase (indicated by the “m” superscript) linked to the fourth nucleoside via a mesylphosphoramidate linkage (indicated by the “z” subscript); the fourth nucleoside comprises a 2’-β-D-deoxyribosyl sugar moiety (indicated by the “d” subscript) and an unmodified guanine nucleobase linked to the fifth nucleoside with a phosphorothioate linkage; and the fifth nucleoside comprises a 2’-β-D-deoxyribosyl sugar moiety and an unmodified cytosine nucleobase; and the compound does not include additional substituents. Herein, sugar, internucleoside linkage, and nucleobase modifications may be indicated within a nucleotide or nucleobase sequence (e.g., by superscript or subscript, as shown above) or may be indicated in text accompanying a sequence (e.g., in separate text that appears within or above or below a table of compounds). Where a specific compound is described herein by way of a drawn chemical structure, each nucleobase, sugar, and internucleoside linkage of such a specific compound includes only the modifications indicated in the drawn chemical structure. One of skill will appreciate, however, that drawn compounds may exist in equilibrium between tautomeric forms and / or as salts in equilibrium with protonated or ionic forms. Drawn structures are intended to capture all such forms of such compounds. While effort has been made to accurately describe compounds in the accompanying sequence listing, should there be any discrepancies between a description in this specification and in the accompanying sequence listing, the description in the specification and not in the sequence listing is the accurate description. The compounds described herein include variations in which one or more atoms are replaced with a non-radioactive isotope or radioactive isotope of the indicated element. For example, compounds herein that comprise hydrogen atoms encompass all possible deuterium substitutions for each of the 1H hydrogen atoms. Isotopic substitutions encompassed by the compounds herein include but are not limited to: 2H or 3H in place of 1H, 13C or 14C in place of 12C, 15N in place of 14N, 17O or 18O in place of 16O, and 33S, 34S, 35S, or 36S in place of 32S. In certain embodiments, non-radioactive isotopic substitutions may impart new properties on the oligomeric agent that are beneficial for use as a therapeutic or research tool. In certain embodiments, radioactive isotopic substitutions may make the compound suitable for research or diagnostic purposes such as imaging. EXAMPLES The following examples illustrate certain embodiments of the present disclosure and are not limiting. Moreover, where specific embodiments are provided, the inventors have contemplated generic application of those specific embodiments. For example, disclosure of an oligonucleotide having a particular motif provides reasonable support for additional oligonucleotides having the same or similar motif. And, for example, where a particular high-affinity modification appears at a particular position, other high-affinity modifications at the same position are considered suitable, unless otherwise indicated. Example 1: Design and Expression of anti-hCD71 VHH domains Phage display was used to identify anti-hCD71 VHH domains. Selected VHH sequences were cloned into pCDNA3.4, with an N-terminal signal peptide derived from human IgG heavy chain (MGWSCIILFLVATATGVHS, SEQ ID NO: 45), a 6xHis tag for purification, and a C-terminal cysteine for conjugation. The sequences of clones B1-VHH and C7-VHH as secreted from CHO cells are shown in Table 4 below. Table 4 Sequences of anti-hCD71 VHH domains as secreted from CHO Compound Amino Acid SequenceSEQ IDNO. VHH clones were expressed in ExpiCHO cells (Thermo Fisher Scientific, #A29133) using the ExpiCHO Expression system, following the maximum titer protocol and according to the manufacturer's recommendations. Twelve days post-transfection, culture supernatants were pooled and centrifuged at 2,000 RCF for 5 minutes to remove cells. The supernatant was then clarified via flocculation: PEG 8000 (3% final concentration) and polydiallyldimethylammonium chloride (0.1% final concentration) were added and the supernatant was incubated for 1 hour at room temperature, followed by 1 hour incubation at 4 ºC. The flocculated supernatant was then centrifuged at 7000 RCF for 10 minutes and the clarified supernatant was filtered using 0.2 µm PES vacuum filter. Protein was purified from the clarified supernatant by standard Protein A affinity chromatography methods, using MabSelect PrismA chromatography resin (Cytiva), high salt HEPES buffered saline (HEPES pH 7.5, 25 mM; NaCl, 500 mM), and elution buffer (NaCl, 100 mM; NaOAc pH 3.5, 100 mM). Eluted fractions were neutralized with 1 M Tris buffer pH 8 and analyzed for protein content by Coomassie Protein Assay (Thermo Fisher Scientific). All fractions with protein were pooled and dialyzed overnight into HEPES buffered saline, HBS (HEPES pH 7.5; NaCl 150 mM), using 3 kDa MW cutoff SnakeSkin dialysis tubing (Thermo Fisher Scientific) and quantified the following day using absorption at 280 nm. Example 2: Design and expression of anti-hCD71 VHH-Fc fusions Anti-hCD71 VHH-Fc fusion proteins were designed and expressed in CHO cells. The anti-hCD71 VHH-Fc fusion proteins comprise a homodimer, wherein each monomer comprises an anti-hCD71 VHH domain fused at the C-terminus to an IgG1 hinge and modified CH2-CH3 (Fc) domain starting at position D221 (Eu numbering); SEQ ID NO: 44. Anti-hCD71 VHH-Fc polypeptides were designed and cloned into a pCDNA3.4 plasmid backbone, with an N-terminal signal peptide derived from human IgG heavy chain (MGWSCIILFLVATATGVHS, SEQ ID NO: 45). The anti-hCD71 VHH-Fc polypeptides contain a “LALA” hinge modifications to ablate immune effector functions (L234A, L235A), “hole” modifications (T366S, L368A and Y407V), a deletion to eliminate the C-terminal lysine (K447), addition of C-terminal LLQGPA to allow site-specific conjugation via MTGase, and a “Thiomab” modification (S239C) to allow site-specific conjugation via a thiol-maleimide reaction. The amino acid sequences of the anti-hCD71 VHH-Fc fusion polypeptides are presented in Table 5, wherein the underlined and italicized amino acids indicate the anti-hCD71 VHH sequence described herein above; the bolded amino acids indicate the “LALA” point modifications; the italicized amino acids indicate the “hole” mutations; the underlined amino acids indicate the modification for site-specific conjugation by MTGase, and the bolded and underlined amino acid indicates the Thiomab modification. Table 5 Sequences of anti-hCD71 VHH-Fc fusion polypeptides as secreted from CHO cells Compound Amino Acid SequenceSEQ IDNO QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPE lasmids, following the procedure described herein above. After 12 days, the culture supernatant was clarified by flocculation, as described above, and purified by standard nickel affinity chromatography methods. Purified protein fractions were pooled and dialyzed overnight into HBS, using 10 kDa MW cutoff SnakeSkin dialysis tubing (Thermo Fisher Scientific) and quantified the following day using absorption at 280 nm. The presence of the anti-hCD71 VHH-Fc homodimer was confirmed by non-denaturing SDS-PAGE. Example 3: Binding affinity of anti-hCD71 VHHs and anti-hCD71 VHH-Fc fusions for human and cyno CD71, determined by nanoBRET A nanoBRET assay was developed to evaluate the binding affinity of anti-hCD71 VHHs and anti- hCD71 VHH-Fc fusions for human and cyno CD71. A human CD71-Nluc fusion protein was constructed by linking NanoLuc (ProMega) through its N- terminal Val to the C-terminal F760 residue of hCD71, using a GGGSGGSSG (SEQ ID NO: 50) flexible linker. A cyno CD71-Nluc fusion protein was constructed in the same manner. The fluorescent VHH tracers B1-VHH- fluor and C7-VHH-fluor were generated by conjugating Alexa594 to the respective anti-hCD71 VHHs via their C-terminal cysteine residues. Crude membrane fractions from HEK293 cells stably expressing hCD71-Nluc or cCD71-Nluc were resuspended in PBS and 100 µL were dispensed into white 96-well assay plates (Thermo Fisher Scientific, #136101) at a concentration of 10,000 cells per well. Membranes were treated with 11.1 µL of B1-VHH-fluor or C7-VHH-fluor at a range of concentrations. The mixtures were incubated for 3 hours at room temperature to reach equilibrium. To initiate BRET, 12.4 µL of 100 µM of the Nluc substrate furimazine was 5 added to each well, and the mixtures were incubated for 5-30 minutes. The assay plate was read on a Promega GlowMax Discover plate reader at wavelengths of 450 nm and 600 nm, and the ratio of emissions at wavelengths 450 / 600 were used to yield %BRET efficiency. Data was subjected to non-linear regression, then fitted to a single site binding hyperbolic function. The dissociation constants (KD) of the fluorescent anti-hCD71 VHH tracers for hCD71 or cCD71 are summarized in Table 6 below. Table 6 KDvalues of fluorescently labeled anti-hCD71 VHHs, determined by nanoBRET Compound hCD71 KD(nM) cCD71 KD(nM) Binding affinities of anti-hCD71 VHHs and VHH-Fc fusions for human and cyno CD71 were measured in a competition assay modified from the previously described assay as follows: 100 µL of crude membrane fractions from stably transfected hCD71-Nluc or cCD71-Nluc HEK293 cells were dispensed into white 96-well assay plates (Thermo Fisher Scientific, #136101). B1-VHH-fluor or C7-VHH-fluor was used as a tracer compound and added to each well at a final concentration of 20 nM. Anti-hCD71 VHHs or VHH-Fc fusion proteins were added at a range of concentrations in triplicate assays points, and the mixtures were incubated for 3 hours at room temperature. BRET was initiated with the addition of furimazine and the assay was completed as described above. Inhibition constants (Ki) were obtained by fitting %BRET efficiency values to a competitive inhibition model, using the KDvalue estimated for B1-VHH-fluor or C7-VHH-fluor, and are presented in Table 7 below. “N.D.” indicates data that was not determined. Table 7 Kivalues of fluorescently labeled anti-hCD71 VHHs and anti-hCD71 VHH-Fc fusions, determined by nanoBRET Compound Tracer hCD71 Ki(nM) cCD71 Ki(nM) B1-VHH B1-VHH-fluor 0.5 N.D. Example 4: Binding affinity of anti-hCD71 VHHs and anti-hCD71 VHH-Fc fusions for human, cyno, and mouse CD71, determined by ELISA The binding affinities of anti-CD71 VHHs and anti-hCD71 VHH-Fc fusions for human, cyno, and mouse CD71 were evaluated by an ELISA binding assay. To estimate ligand affinity by ELISA, the recombinant ectodomains of human, cyno, and mouse CD71 were immobilized by adding 25 µL of 4 µg / ml ectodomain in carbonate buffer to individual wells of a 384 well MaxiSorp plate (Thermo Fisher Scientific, #464718) and incubating overnight at 4 ºC. The next day the plates were washed once with PBS and blocked with the addition of 100 µL 1% casein (Thermo Fisher Scientific, #37528) followed by 1 hour incubation. The plates were then washed once with PBS, followed by addition of 25 µL / well of a 12-point series (1 / 3 dilution series from 1000 nM to 0.0056 nM) of the respective ligand in PBS to duplicate wells. Plates were incubated with the ligands for 2 hours, then washed 8 times in PBS with 0.1% Tween, and tapped dry. Wells containing anti-hCD71 VHH were treated with a 1:5000 dilution of HRP labeled anti-Myc tag antibody (Abcam, #1326). Wells containing anti-hCD71 VHH-Fc were treated with a 1:13000 dilution of HRP labeled goat anti-human (Jackson ImmunoResearch, #109-035-003). Plates were incubated with the secondary antibody for 1 hour, followed by 8 washes in PBS with 0.1% Tween. For ELISA development, 25 µL of TMB substrate (Thermo Fisher Scientific, #34028) was added to each well and allowed to develop until the highest concentration wells turned moderate-deep blue (typically 5- 15 minutes). Then, 25 µL of 2N H2SO4was added per well to stop the reaction. Absorbance was measured at 450 nm on a Tecan Spark Microplate Reader instrument. The resulting values were fitted to a 4-parameter variable slope dose- response model using GraphPad Prism 9 software (GraphPad Software, San Diego, CA) to derive EC50values. Table 8 KDvalues of fluorescently labeled anti-hCD71 VHHs and anti-hCD71 VHH-Fc fusions for human, cyno, and mouse CD71, determined by ELISA Compound hCD71 EC50(nM) cCD71 EC50(nM) mCD71 EC50(nM) B1-VHH 2.1 6.5 >3000 E ed to an anti-hCD71 VHH domain Oligomeric compounds comprising an antisense oligonucleotide complementary to a mouse HPRT nucleic acid, and a sense oligonucleotide complementary to the antisense oligonucleotide were designed as follows, then conjugated to anti-hCD71 VHH domain. Design of Antisense Oligonucleotide Antisense oligonucleotide Compound No. 1586322 is 23 nucleosides in length and is complementary to mouse HPRT. Compound No. 1586322 has a nucleobase sequence described in the table below, wherein each cytosine residue in the compound is non-methylated; has a sugar motif as designated in the column labeled “Sugar Motif (5’ to 3’)”, wherein each “e” represents a 2’-MOE sugar moiety, each “y” represents a 2’-OMe sugar moiety, and each “f” represents a 2’-F sugar moiety; and has an internucleoside linkage motif as designated in the column labeled “Internucleoside Linkage (5’ to 3’)”, wherein each “o” represents a phosphodiester internucleoside linkage, and each “s” represents a phosphorothioate internucleoside linkage. The antisense oligonucleotide has a vinyl phosphonate moiety on the 5’ end. Compound No. 1586322 was previously disclosed in International Patent No. WO 2022 / 174053. Table 9 Design of an antisense oligonucleotide complementary to human HPRT1 Compound Sequence (5’ to 3’)Sugar Motif Internucleoside SEQ O. Design of Sense Oligonucleotides The sense oligonucleotides described in the table below are 21 nucleosides in length and are complementary to the first 21 nucleosides of the antisense oligonucleotide (from 5’ to 3’) wherein the last two 3’-nucleosides of the antisense oligonucleotides are not paired with the sense oligonucleotide (are overhanging nucleosides). The sense oligonucleotides have a sugar motif as designated in the column labeled “Sugar Motif (5’ to 3’)”, wherein each “y” represents a 2’-OMe sugar moiety, and each “f” represents a 2′-F sugar moiety; and an internucleoside linkage motif as designated in the column labeled “Internucleoside Linkage (5’ to 3’)”, wherein each “o” represents a phosphodiester internucleoside linkage, and each “s” represents a phosphorothioate internucleoside linkage. Compound No. 1590184 has a 6-amino-2-(hydroxymethyl)hexyl phosphoryl (3nC7) linker at the 3’ end, as shown below: Compound No.1615206 has hexyl phosphoryl (3nC7-C3-maleimide) linker at the 3’ end, as shown below: Design of sense oligonucleotides Compound 3’ Sugar Mot Internucleoside Se uence (5’ to 3’)if Linkages SEQ O. Sense oligonucleotide Compound No. 1615206 was prepared from Sense Compound No. 1590184 as follows. A solution of Compound No.1590184 (1 eq., 4.2 µmol, 30 mg) dissolved in 0.05 M sodium phosphate buffer pH 7.0 (1 mL) was added to a solution of maleimidopropionyl-NHS ester (5 eq., 21 µmol, 5.59 mg) dissolved in DMSO (0.5 mL). The reaction mixture was stirred for 2 hours at room temperature, with reaction monitoring by LC-MS. The crude reaction was purified by SAX HPLC on an AP-2 glass column (20 mm × 100 mm) using a gradient of mobile phase A (100 mM NH4OAc in 30% aq. MeCN) and mobile phase B (100 mM NH4OAc, 1.5 M NaBr in 30% aq. MeCN). The purified compound was desalted by standard RP HPLC (C18 column, water / MeCN) to yield Compound No.1615206 (78% yield, 3.3 µmol, 24 mg). Design of Oligomeric Duplex Oligomeric duplex compounds prepared with antisense oligonucleotide compound numbers and corresponding sense oligonucleotide compound numbers are listed in the table below. Table 11 Design of an oligomeric duplex targeted to human HPRT1 Duplex Compound No. Antisense Compound No. Sense Compound No. 1801111 1586322 1615206 Preparation of oligomeric duplex conjugated to anti-hCD71 VHH domain Compound No. B1-VHH-1801111 was synthesized from oligomeric duplex Compound No.1801111 and B1-VHH (described in Example 1) as shown in the scheme above. A solution of TCEP-HCl in PBS (10 eq., 4 mM, 1.45 mL) was added to B1-VHH in PBS (1 eq., 1.95 mg / mL, 5 mL), and the reaction mixture was incubated for 1 hour at room temperature. Compound No.1801111 in 50 mM PBS pH 7.4 (1.2 eq., 4 mM, 175 µL) was then added directly to the reaction mixture. The reaction mixture was mixed for 3 hours at room temperature, then overnight at 4 ºC.100 mM DHAA in PBS (0.5 mL) was added, and the reaction mixture was further incubated for 3 hours at room temperature, then overnight at 4 ºC. The crude reaction mixture was filtered and purified by Immobilized Metal Affinity Chromatography (IMAC) using a HisTrap Fast Flow Crude 5 mL column (Cytiva, #17-5286-01), a flow rate of 1 mL / mL, binding buffer (1 × PBS, pH 7.4), and elution buffer (1 × PBS, 500 mM imidazole, pH 7.4). Collected fractions were filtered through a Pierce Protein Concentrator PES 10K MWCO, 5- 20 mL (ThermoFisher Scientific, # 88527), washed with PBS, and resuspended in PBS in a 1.5 mL Protein LoBind Tube (Eppendorf, #022431081) to yield Compound No. B1- VHH-1801111 (0.331 mM, 0.6 mL, overall yield: 35%). Compound No. C7-VHH-1801111 was synthesized from C7-VHH and Compound No.1801111 following the same procedure as Compound No. B1-VHH-1801111. Example 6: Effects of oligomeric duplexes conjugated to VHH domains on mouse HPRT mRNA levels in hTfRKI / +knock in mice hTfRKI / +knock in mice (Taconic Biosciences) were used to determine effects of oligomeric duplexes conjugated to VHH peptides described above on mouse HPRT. Human transferrin receptor (hTFR) / CD71 knock-in mice have the coding region of mouse exon 2 as well as the splice donor-site of mouse intron 2 replaced with the human TFR open reading frame according to NCBI transcript NM_001128148.2. Humanization of the transferrin receptor gene was done via CRISPR / Cas-9-mediated gene editing, allowing for generation of a model with constitutive expression of humanized transferrin receptor gene. Targeting strategy was based on NCBI transcripts NM_011638.4 (mouse) and NM_001128148.2 (human). A plasmid allowing expression of Cas9 mRNA, specific gRNA, and the puromycin resistance cassette; and a plasmid containing the homology regions of the mouse transferrin receptor gene, an FRT site, and the replaced human region were co-transfected into the Taconic Biosciences C57BL / 6N Tac ES cell line. The humanized mice are called hTfRKI / +knock-in mice. They express one copy of the mouse TFR gene and one copy of the humanized TFR gene under the control of the endogenous mouse promoter. Treatment hTfRKI / +knock in mice were divided into groups of 4 mice each. Mice received intravenous injections of oligomeric duplexes conjugated to VHH domains at various doses indicated in the tables below on Day 1 and Day 8 (a total of 2 treatments). Doses are expressed in the tables below as the equivalent dose of unconjugated oligomeric duplex in mg / kg. One group of 4 mice received intravenous injections of PBS on Day 1 and Day 8 (a total of 2 treatments) as a negative control. RNA analysis Mice were sacrificed on Day 22 and RNA was extracted from mouse quadriceps (quad), gastrocnemius (gastroc), heart, liver, cortical tissue, and spinal cord for real-time RTPCR analysis of mouse HPRT RNA expression. Mouse HPRT primer probe RTS43125 (forward sequence CTCCTCAGACCGCTTTTTGC, designated herein as SEQ ID NO: 60; reverse sequence TAACCTGGTTCATCATCGCTAATC, designated herein as SEQ ID NO: 61; probe sequence CCGTCATGCCGACCCGCAGT, designated herein as SEQ ID NO: 62) was used to measure mouse HPRT RNA levels. Results are presented as percent mouse HPRT relative to the amount of HPRT in PBS treated control animals, normalized to mouse GAPDH (% control). Mouse GAPDH was amplified using mouse primer probe set mGapdh_LTS00102 (forward sequence GGCAAATTCAACGGCACAGT, designated herein as SEQ ID NO: 63; reverse sequence GGGTCTCGCTCCTGGAAGAT, designated herein as SEQ ID NO: 64; probe sequence AAGGCCGAGAATGGGAAGCTTGTCATC, designated herein as SEQ ID NO: 65). Table 12 Reduction of mouse HPRT mRNA in hTfRKI / +knock in mice HPRT RNA (% control) Compound Dose N k r Example 7: Design and synthesis of unconjugated siRNA targeted to HPRT1 nucleic acid Antisense RNAi oligonucleotide 1586322 (described herein above) was paired with a sense RNAi oligonucleotide to generate an siRNA duplex as described below. Design of Sense Oligonucleotide Compound No.1586323 is 21 nucleosides in length and is complementary to the first 21 nucleosides of the antisense oligonucleotide Compound No.1586322 (from 5’ to 3’) wherein the last two 3’-nucleosides of the antisense oligonucleotides are not paired with the sense oligonucleotide (are overhanging nucleosides). Compound No.1586323 has a sugar motif as described in the table below in the column labeled “Sugar Motif (5’ to 3’)”, wherein each ‘y’ represents a 2’-OMe sugar moiety, and each ‘f’ represents a 2’-F sugar moiety; and an internucleoside linkage motif as described in the column labeled “Linkages (5’ to 3’)”, wherein each ‘o’ represents a phosphodiester internucleoside linkage, and each ‘s’ represents a phosphorothioate internucleoside linkage. Table 13 Design of sense RNAi oligomeric compounds Compound No. SequenceSugar Motif Linkages SEQ ID (5’ to 3’)(5’ to 3’) (5’ to 3’) NO. De s g o up e es In order to form siRNA, duplexes were prepared by pairing an antisense RNAi oligonucleotide with a sense RNAi oligonucleotide, and the resulting siRNA duplex Compound No. or identifier is described in the table below. Duplex No.1588821 was previously disclosed in International Patent No. WO 2022 / 174053. Table 14 Oligomeric duplexes targeted to human HPRT1 Duplex ID Antisense Compound No. Sense Compound No. / ID 1588821 1586322 1586323 Example 8: Effect of unconjugated oligomeric duplex on mouse HPRT mRNA levels in hTFRKI / +knock in mice hTfRKI / +knock in mice (Taconic Biosciences) described above were used to determine effects of unconjugated oligomeric duplex on mouse HPRT RNA. Treatment hTFRKI / +mice were divided into groups of 4 mice each. A group of 4 mice received an intravenous administration of unconjugated oligomeric duplex, Compound No. 1588821, on Day 1 and Day 8 (for a total of 2 treatments) at a dose of 30 mg / kg. A group of 4 mice received PBS as a negative control. RNA analysis The mice were sacrificed on Day 22, and RNA was extracted from quadriceps (Quad), heart, gastrocnemius (gastroc), liver, cortical tissue, spinal cord, and sciatic nerve for quantitative real time RTPCR analysis to measure amount of mouse HPRT1 RNA using mouse primer probe set RTS43125 (described herein above). Results are presented as percent mouse HPRT RNA relative to the amount of HPRT RNA in PBS treated control animals, normalized to mouse GAPDH (% control). Mouse GAPDH was amplified using mouse primer probe set mGapdh_LTS00102 (described herein above). Table 15 Reduction of mouse HPRT mRNA in hTfRKI / +knock in mice Compound HPRT1 RNA (% control) o.CoDose Nnjugate(mg / kg) Quad Heart Gastroc Liver

Claims

1. CLAIMS 1. A polypeptide comprising a VHH domain that binds transferrin receptor (TfR), wherein the VHH domain comprises: CDR1 comprising the amino acid sequence of SEQ ID NO: 14 with no more than 2 substitutions or no more than 1 substitution; CDR2 comprising the amino acid sequence of SEQ ID NO: 16 with no more than 2 substitutions or no more than 1 substitution; and CDR3 comprising the amino acid sequence of SEQ ID NO: 18 with no more than 2 substitutions or no more than 1 substitution; OR CDR1 comprising the amino acid sequence of SEQ ID NO: 24 with no more than 2 substitutions or no more than 1 substitution; CDR2 comprising the amino acid sequence of SEQ ID NO: 26 with no more than 2 substitutions or no more than 1 substitution; and CDR3 comprising the amino acid sequence of SEQ ID NOs: 28 with no more than 2 substitutions or no more than 1 substitution.

2. The polypeptide of claim 1, wherein the VHH domain comprises: CDR1 comprising the amino acid sequence of SEQ ID NO: 14; CDR2 comprising the amino acid sequence of SEQ ID NO: 16; and CDR3 comprising the amino acid sequence of SEQ ID NO: 18; Or CDR1 comprising the amino acid sequence of SEQ ID NOs: 24; CDR2 comprising the amino acid sequence of SEQ ID NOs: 26; and CDR3 comprising the amino acid sequence of SEQ ID NOs:

28.

3. The polypeptide of claim 1 or claim 2, wherein the VHH domain has at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to SEQ ID NO: 11 or 12.

4. The polypeptide of claim 1 or claim 2, wherein the VHH domain has at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to SEQ ID NO: 21 or 22.

5. The polypeptide of any one of claims 1-4, consisting of the VHH domain.

6. The polypeptide of any one of claims 1-4, wherein the polypeptide comprises an N-terminal extension.

7. The polypeptide of any one of claims 1-4 and 6, wherein the polypeptide comprises a C-terminal extension.

8. The polypeptide of claim 6 or 7, wherein the N-terminal extension and / or the C-terminal extension comprises a reactive moiety.

9. The polypeptide of claim 8, wherein the reactive moiety is a free cysteine.

10. The polypeptide of any of claims 1-4 or 6-9, wherein the polypeptide comprises a Fc polypeptide.

11. The polypeptide of claim 10, wherein the VHH domain is attached at its N-terminus to the C- terminus of the Fc polypeptide.

12. The polypeptide of claim 10, wherein the VHH domain is attached at its C-terminus to the N- terminus of the Fc polypeptide.

13. The polypeptide of claim 10, wherein the VHH domain is attached at its N-terminus to a side chain of the Fc polypeptide.

14. The polypeptide of claim 10, wherein the VHH domain is attached at its C-terminus to a side chain of the Fc polypeptide.

15. The polypeptide of any one of claims 10-14, wherein the VHH domain is directly attached to the f Fc polypeptide.

16. The polypeptide of any one of claims 10-14, wherein the VHH domain is attached through a linker to the Fc polypeptide.

17. The polypeptide of any one of claims 1-4 or 6-16, wherein the polypeptide comprises one or two VHH domains.

18. A polypeptide dimer comprising a first polypeptide and a second polypeptide, wherein the first polypeptide is a polypeptide of any one of claims 11-16 comprising a first Fc polypeptide and the second polypeptide comprises a second Fc polypeptide.

19. The polypeptide dimer of claim 18, wherein the polypeptide dimer comprises exactly one VHH domain.

20. The polypeptide dimer of claim 18, wherein the sequence of the first Fc polypeptide is identical to the sequence of the second Fc polypeptide.

21. The polypeptide dimer of claim 18, wherein the sequence of the first Fc polypeptide and the sequence of the second Fc polypeptide are different.

22. The polypeptide dimer of claim 21, wherein the first Fc polypeptide and the second Fc polypeptide form a knob-in-hole heterodimer.

23. The polypeptide dimer of any one of claims 18-22, wherein the first Fc polypeptide comprises a sequence having at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO:

44.

24. The polypeptide dimer of any one of claims 18-22, wherein the second Fc polypeptide comprises a sequence having at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO:

44.

25. The polypeptide dimer of any of claims 18-22, wherein at least one Fc polypeptide has at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% sequence identity to any of SEQ ID NO: 4-9 or 35-44.

26. The polypeptide dimer of any of claims 18-22, wherein each Fc polypeptide has at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% sequence identity to any of SEQ ID NO: 4-9 or 35-44.

27. The polypeptide dimer of any one of claims 18-26, wherein the second polypeptide does not comprise an antigen binding domain.

28. The polypeptide dimer of any one of claims 18-26, wherein the second polypeptide comprises a VHH domain that binds TfR 29. The polypeptide dimer of any one of claims 18-28, which is a heterodimer.

30. The polypeptide dimer of any one of claims 18, 20, 23-26 or 28, which is a homodimer.

31. The polypeptide dimer of any one of claims 18-30, wherein the second polypeptide is a polypeptide of any one of claims 10-16, and wherein the first polypeptide and the second polypeptide are the same or different.

32. The polypeptide dimer of any of claims 18-31, wherein neither Fc polypeptide comprises a transferrin receptor binding moiety.

33. A delivery complex comprising a polypeptide of any of claims 1-17 or the polypeptide dimer of any one of claims 18-32, and at least one cargo.

34. The delivery complex of claim 33, wherein the cargo is selected from an oligomeric agent, a peptide, a protein, a chromophore, a small molecule, an antibody or antibody fragment, or a lipid.

35. The delivery complex of claim 33 or 34, wherein the cargo is an oligomeric agent comprising at least one modified oligonucleotide.

36. The delivery complex of claim 35, wherein the at least one modified oligonucleotide is covalently attached to the VHH domain.

37. The delivery complex of any one of claims 35-36, wherein the delivery complex comprises exactly one modified oligonucleotide.

38. The delivery complex of any one of claims 35-36, wherein the delivery complex comprises a second modified oligonucleotide.

39. The delivery complex of claim 38, wherein the second modified oligonucleotide is covalently attached to the VHH domain.

40. The delivery complex of claim 38 or 39, wherein the second modified oligonucleotide forms a duplex with the first modified oligonucleotide.

41. The delivery complex of any one of claims 33-40 having a ratio of two VHH domains to one oligomeric agent.

42. The delivery complex of any one of claims 33-40 having a ratio of one oligomeric agent to one VHH domain.

43. The delivery complex of any one of claims 33-40, having a ratio of two oligomeric agents to one VHH domain.

44. The delivery complex of any one of claims 33-43, wherein the at least one modified oligonucleotide is covalently attached to the first and / or second Fc polypeptide.

45. The delivery complex of claim 44, wherein the delivery complex comprises exactly one modified oligonucleotide.

46. The delivery complex of claim 45, wherein the delivery complex comprises a second modified oligonucleotide.

47. The delivery complex of claim 46, wherein the second modified oligonucleotide is covalently attached to the first Fc polypeptide.

48. The delivery complex of claim 46 or 47, wherein the second modified oligonucleotide forms a duplex with the first modified oligonucleotide.

49. The delivery complex of any of claims 46-48, having a ratio of one oligomeric agent to one modified Fc domain .

50. The delivery complex of any of claims 46-49, having a ratio of two oligomeric agents to one modified Fc domain.

51. The delivery complex of any of claims 33-49, wherein the at least one modified oligonucleotide is attached to the polypeptide or polypeptide dimer of any of claims 1-32 through a click reaction.

52. The delivery complex of claim 51, wherein the at least one modified oligonucleotide is attached to an Fc domain through a glutamine, optionally Q76, based on the numbering of SEQ ID NO:

51.

53. The delivery complex of any of claims 33-52, wherein the first modified oligonucleotide consists of 15-30 linked nucleosides.

54. The delivery complex of any of claims 33-53, wherein the first modified oligonucleotide comprises a targeting region comprising at least 12 contiguous nucleosides, wherein the nucleobase sequence of the targeting region is at least 80% complementary to the nucleobase sequence of an equal-length target region of a target nucleic acid, and wherein the sugar moiety of at least one nucleoside of the first modified oligonucleotide is a modified sugar moiety and / or at least one internucleoside linkage of the first modified oligonucleotide is a modified internucleoside linkage.

55. The delivery complex of claim 54, comprising a second modified oligonucleotide, wherein the second oligonucleotide consists of 15-30 linked nucleosides.

56. The delivery complex of claim 54 or 55, wherein the first and / or second modified nucleoside comprises a modified sugar moiety.

57. The delivery complex of claim 56, wherein the modified sugar moiety comprises a bicyclic sugar moiety.

58. The delivery complex of claim 57, wherein the bicyclic sugar moiety comprises a 2’-4’ bridge selected from -O-CH2-; and -O-CH(CH3)-.

59. The delivery complex of any of claims 56-58, wherein the modified nucleoside comprises a non- bicyclic modified sugar moiety.

60. The delivery complex of claim 59, wherein the non-bicyclic modified sugar moiety is a 2’-MOE sugar moiety, a 2’-OMe sugar moiety, or a 2’-F sugar moiety.

61. The delivery complex of any of claims 56-60, wherein the modified nucleoside comprises a sugar surrogate.

62. The delivery complex of any of claims 58-61, wherein the first and / or second modified oligonucleotide comprises at least one modified internucleoside linkage.

63. The delivery complex of claim 62, wherein at least one modified internucleoside linkage is a phosphorothioate internucleoside linkage or a mesyl phosphoramidate internucleoside linkage.

64. The delivery complex of any of claims 62-63, wherein each internucleoside linkage is independently selected from a phosphodiester internucleoside linkage, a phosphorothioate internucleoside linkage, and a mesyl phosphoramidate internucleoside linkage.

65. The delivery complex of any of claims 62-64, wherein at least one nucleoside of the modified oligonucleotide comprises a modified nucleobase.

66. The delivery complex of claim 65, wherein the modified nucleobase is a 5-methylcytosine.

67. The delivery complex of any of claims 54-66, wherein the first and / or the second modified oligonucleotide comprises a deoxy region.

68. The delivery complex of claim 67, wherein each nucleoside of the deoxy region is a 2’-β-D- deoxynucleoside.

69. The delivery complex of claim 67 or claim 68, wherein the deoxy region consists of 6, 7, 8, 9, 10, or 6-10 linked nucleosides.

70. The delivery complex of any of claims 67-69, wherein each nucleoside immediately adjacent to the deoxy region comprises a modified sugar moiety.

71. The delivery complex of any of claims 67-70, 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.

72. The delivery complex of claim 71, wherein each nucleoside of the 5’-region comprises a modified sugar moiety.

73. The delivery complex of claim 71 or claim 72, wherein each nucleoside of the 3’-region comprises a modified sugar moiety.

74. The delivery complex of claim 55, wherein the second modified oligonucleotide comprises a duplexing region comprising at least 12 contiguous nucleosides, wherein the nucleobase sequence of the duplexing region is at least 80% complementary to the nucleobase sequence of an equal length sequence of the first modified oligonucleotide.

75. The delivery complex of claim 74, wherein the nucleobase sequence of the duplexing region of the second modified oligonucleotide is at least 85%, at least 90%, at least 95%, or 100% complementary to the nucleobase sequence of an equal length sequence of the first modified oligonucleotide.

76. The delivery complex of claim 74 or 75, wherein the second modified oligonucleotide consists of the duplexing region.

77. The delivery complex of any one of claims 74-76, wherein each sugar moiety of the first modified oligonucleotide and the second modified oligonucleotide is selected from a 2’-F sugar moiety, a 2’- OMe sugar moiety, a DNA sugar moiety, a 2’-NMA sugar moiety, a 2’-MOE sugar moiety, and a FHNA sugar surrogate.

78. The delivery complex of claim 77, wherein the first modified oligonucleotide consists of 23 linked nucleosides and the second modified oligonucleotide consists of 21 linked nucleosides.

79. The delivery complex of claim 78, wherein the nucleosides at position 2 and the nucleoside at position 14 of the first modified oligonucleotide, counting from the 5’-end, comprise 2’-F sugar moieties.

80. The delivery complex of claim 78, wherein at least 2 of the nucleosides at positions 7, 9, 10, and 11 of the second modified oligonucleotide, counting from the 5’-end, comprise 2’-F sugar moieties.

81. The delivery complex of claim 79 or 80, wherein at least 50%, at least 60%, at least 70%, at least 75%, or at least 80% of the nucleosides of the first modified oligonucleotide and / or the second modified oligonucleotide comprise a 2’-OMe sugar moiety.

82. The delivery complex of claim 79 or 80, wherein fewer than 20%, fewer than 15%, or fewer than 10% of the nucleosides of the first modified oligonucleotide and / or the second modified oligonucleotide comprise a 2’-F sugar moiety.

83. The delivery complex of any of claims 74-82, wherein the first modified oligonucleotide comprises a stabilized phosphate group attached to the 5’-terminal nucleoside.

84. The delivery complex of claim 83, wherein the stabilized phosphate group comprises an (E)-vinyl phosphonate.

85. The delivery complex of any of claims 58-78 or 83-84, wherein the first and / or second modified oligonucleotide consists of 12-30, 12-22, 12-20,14-18, 14-20, 15-17, 15-25, 16-20, 18-22, 19-21, 21- 23, or 18-20 linked nucleosides.

86. An isolated nucleic acid that encodes the polypeptide of any one of claims 1-17.

87. An expression vector comprising the isolated nucleic acid of claim 86.

88. A host cell comprising the nucleic acid of claim 86 or the expression vector of claim 87.

89. A method of producing the polypeptide of any one of claims 1-17, comprising incubating the host cell of claim 88 under conditions suitable to express the polypeptide.

90. The method of claim 89, further comprising isolating the polypeptide.

91. An isolated nucleic acid comprising a first polynucleotide sequence encoding the first polypeptide of the polypeptide dimer of any one of claims 18-32 and a second polynucleotide sequence encoding the second polypeptide of the polypeptide dimer of any one of claims 18-32.

92. An expression vector comprising the nucleic acid of claim 91.

93. A host cell comprising the nucleic acid of claim 91 or the expression vector of claim 92.

94. A host cell that expresses the polypeptide dimer of any one of claims 18-32.

95. A method of producing the polypeptide dimer of any one of claims 18-32, comprising incubating the host cell of claim 93 or claim 94 under conditions suitable to express the polypeptide dimer.

96. The method of claim 95, further comprising isolating the polypeptide dimer.