Cell-targeting complexes and uses thereof

Abstract

Provided are complexes and methods for targeting cells of interest for delivery of a cargo such as an oligomeric compound or an oligomeric duplex. In particular, the complex may comprise a transferrin receptor binding moiety and a half-life extension moiety.

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 CORE0175SEQ.xml created October 1, 2024, which is 5,793 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 complexes and methods for targeting cells of interest with a cargo. 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 agents, including antibodies, antibody fragments, and peptides, have potential to deliver oligonucleotides, cytotoxic drugs, antibodies, and antibody fragments across the BBB into the CNS. 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 complexes comprising a transferrin receptor binding moiety, a half-life extension moiety, and an cargo, for example, an oligomeric agent. In certain embodiments, the transferrin receptor binding moiety, half-life extension moiety, and cargo are joined by one or more linkers and / or branching groups. In certain embodiments, the complex comprises exactly one transferrin receptor binding moiety. In certain embodiments, the transferrin receptor binding moiety is a peptide or protein. In certain embodiments, the transferrin receptor binding moiety is a bicyclic peptide. In certain embodiments, the transferrin receptor binding moiety is a VHH or VNAR. In certain embodiments, the complex comprises exactly one half-life extension moiety. In certain embodiments, the complex comprises more than one half-life extension moieties. In certain embodiments, the half-life extension moiety is an albumin-binding moiety, an FcRn-binding moiety, or an IgG-binding moiety. In certain embodiments, the half-life extension moiety is a peptide, a protein, or a fatty acid. In certain embodiments, the half-life extension moiety is an albumin-binding cyclic peptide. In certain embodiments, the half-life extension moiety comprises C18 diacid. In certain embodiments, the complex comprises a hydrophilic moiety. In certain embodiments, the cargo is an oligomeric agent. In certain embodiments, the oligomeric agent is an oligomeric compound comprising an antisense oligonucleotide. In certain embodiments, the oligomeric agent is an oligomeric duplex comprising an antisense oligomeric compound comprising an antisense oligonucleotide and a sense oligomeric compound comprising a sense oligonucleotide. Brief Description of the Drawings Figure 1 shows mouse plasma concentrations of B191 over time. Figure 2 shows mouse plasma concentrations of B192 over time. Figure 3 shows mouse plasma concentrations of B193 over time. 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. As used herein, the use of “or” means “and / or” unless stated otherwise. Furthermore, the use of the term “including” as well as other forms, such as “includes” and “included”, is not limiting. 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’-H(H) deoxyfuranosyl sugar moiety. In certain embodiments, a 2’-deoxynucleoside is a 2’-β-D-deoxynucleoside and comprises a 2’-β-D-deoxyribosyl sugar moiety, which has the β-D ribosyl configuration as found in naturally occurring deoxyribonucleic acids (DNA). In certain embodiments, a 2’-deoxynucleoside may comprise a modified nucleobase or may comprise an RNA nucleobase (uracil). As used herein, “2’-MOE” means a 2’-OCH2CH2OCH3group in place of the 2’-OH group of a 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 configuration. “MOE” means O-methoxyethyl. As used herein, “2’-MOE nucleoside” means a nucleoside comprising a 2’-MOE sugar moiety. As used herein, “2’-OMe” means a 2’-OCH3group in place of the 2’-OH group of a furanosyl sugar moiety. A“2’-O-methyl sugar moiety” or “2’-OMe 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 configuration. As used herein, “2’-OMe nucleoside” means a nucleoside comprising a 2’-OMe sugar moiety. As used herein, “2’-F” means a 2’-F group in place of the 2’-OH group of a furanosyl sugar moiety. A“2’-fluoro sugar moiety” or “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 –O-CH2-C(=O)-NH-CH3group in place of the 2’-OH group of a ribosyl sugar moiety. A “2’-NMA sugar moiety” is a sugar moiety with a 2’–O-CH2-C(=O)-NH-CH3group in place of the 2’-OH group of a ribosyl sugar moiety. Unless otherwise indicated, a 2’-NMA sugar moiety is in the β-D configuration. “NMA” means O-(N-methyl)acetamide. As used herein, “2’-NMA nucleoside” means a nucleoside comprising a 2’-NMA sugar moiety. As used herein, “2’-substituted nucleoside” means a nucleoside comprising a 2’-substituted sugar moiety. As used herein, “2’-substituted” in reference to a sugar moiety means a sugar moiety comprising at least one 2'- substituent group other than H or OH. As used herein, “5-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, “administering” means providing a complex or pharmaceutical composition comprising a complex to a subject. As used herein, an “aliphatic amino acid” is an amino acid having a side chain composed of an alkyl group. Aliphatic amino acids include, but are not limited to, glycine, alanine, leucine, isoleucine, valine, beta-alanine, 2-aminoisobutyric acid. As used here in, an “amino acid” is a compound or a monomer subunit of a peptide or polypeptide having an amino group, a carboxylate group, and at least one carbon covalently linked between the amino group and carboxylate group that comprises an optional side chain. An “α-amino acid” contains exactly one carbon between the amino group and carboxylate group that bears an optional side chain. A “β-amino acid” contains exactly two optionally substituted carbons between the amino group and the carboxylate group. Amino acids include non-natural amino acids as defined herein. As used herein, an “amino acid mimetic” is a compound or a monomer subunit of a peptidomimetic having an amino group surrogate, a carboxylate group surrogate, and at least one carbon covalently linked between the amino group surrogate and carboxylate group surrogate that comprises an optional side chain. As used herein, an “aromatic amino acid” is an amino acid having an aromatic ring in its side chain. Aromatic amino acids include, but are not limited to, phenylalanine, tyrosine, and tryptophan. As used herein, “bicycle ligand” means a ligand comprising a polypeptide or peptidomimetic covalently bound to a molecular scaffold at three distinct sites, forming two polypeptide loops. Typically, such peptides or peptidomimetics comprise a peptide or polypeptide having natural or non-natural amino acids or amino acid mimetics, including a first, a second, and a third amino acid comprising reactive groups that form covalent bonds to the scaffold. In certain embodiments, the peptides or peptidomimetics comprise at least three cysteine residues (referred to herein as Ci, Ciiand Ciii), which are the reactive groups. As used herein, “loop polypeptide” refers to the portion of the bicycle ligand that forms the two polypeptide loops, including the reactive groups, but excluding any N-terminal or C-terminal extensions. As used herein, “loop sequences” refers to the amino acids or amino acid mimetics between the reactive groups. As used herein, “bicyclic peptide” means any polypeptide that forms two polypeptide loops. A bicyclic peptide may or may not include a non-peptidic molecular scaffold. As used herein, “bicyclic nucleoside” or “BNA” means a nucleoside comprising a bicyclic sugar moiety. As used herein, “bicyclic sugar” or “bicyclic sugar moiety” means a modified sugar moiety comprising two rings, wherein the second ring is formed via a bridge connecting two of the atoms in the first ring thereby forming a bicyclic structure. In certain embodiments, the first ring of the bicyclic sugar moiety is a furanosyl moiety. In certain embodiments, the bicyclic sugar moiety does not comprise a furanosyl moiety. As used herein, “cell-targeting moiety” means a group of atoms that is capable of binding to a particular cell type or particular cell types. In certain embodiments, a cell-targeting moiety is capable of binding the cell-surface receptor or the cell-surface moiety. In certain embodiments, a cell-targeting moiety is 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 comprises a cyclic peptide, a bicyclic peptide, a linear peptide, an aptamer, an antibody, or a fragment thereof. 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. In certain embodiments, a portion of the cell-surface moiety is 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. In certain embodiments, the cell-surface receptor is the transferrin 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, “complementary nucleobase(s)” or “complementary” in reference to nucleobase(s) 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 sequence(s)” or “complementary” in reference to sequence(s) refers to two nucleobase sequences in which some, a majority, 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, “complex” means a molecule having more than one region, or one or more non- covalently associated molecules that are associated with each other through hydrogen bonding, electrostatic attraction, and / or van der Waals forces. In certain embodiments, a complex comprises an oligomeric duplex. As used herein, "contiguous" in the context of an oligonucleotide refers to nucleosides, nucleobases, sugar moieties, or internucleoside linkages that are immediately adjacent to each other. For example, “contiguous nucleobases” means nucleobases that are immediately adjacent to each other in a sequence. As used herein, a “cyclic amino acid” is an amino acid where the side chain connects to the backbone amide to form a cyclic structure. “Cyclic amino acid” includes, but is not limited to, proline or hydroxyproline. As used herein, “cyclic peptide” means a polypeptide comprised of natural amino acids and optionally non-natural amino acids or amino acid mimetics, and having at least one loop having at least two amino acids. A bicyclic peptide is a cyclic peptide comprising two loops. A bicyclic peptide may comprise a first, a second, and a third amino acid comprising reactive groups that form covalent bonds to a scaffold. As used herein, “loop polypeptide” refers to the portion of the cyclic peptide that forms the polypeptide loop, including the reactive groups, but excluding any N-terminal or C-terminal extensions. As used herein, “loop sequences” refers to the sequence of amino acids or amino acid mimetics between the reactive groups. As used herein, “Fab” or “Fab fragment” means a heterodimeric polypeptide corresponding to the region of a primate (human) or rodent antibody containing variable domains that can be derived from papain digestion of the whole antibody. A Fab may also be expressed recombinantly. A Fab contains one variable domain (VH) and one constant domain (CH1) of the heavy chain and one light chain, including one variable domain (VL) and one constant domain (CL). Each variable domain includes three complementarity- determining regions, or CDRs. As used herein, a “standard Fab” consists of a dimer of one heavy chain (VH + CH1), and a light chain (VL+CL), attached to the heavy chain via a disulfide bond, when attached at the C- terminal end of its CH1 domain to the N-terminal of a hinge-region / CH2 domain of an Fc domain as defined herein. As used herein, “F(ab’)2” means a polypeptide corresponding to the region of a primate (human) or rodent antibody that can be derived from pepsin digestion of the whole antibody. A F(ab’)2may also be expressed recombinantly. A F(ab’)2contains a disulfide-linked pair of Fabs. In certain embodiments, a recombinant F(ab’)2may be bispecific, with each Fab recognizing a different antigen. As used herein, “scFv” or “single-chain variable fragment” means a monomeric polypeptide consisting of the variable domain of a light chain appended at the N-terminus or C-terminus of the variable domain of a heavy chain of a mammalian IgG antibody. As used herein, “Fc domain” means a protein 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. 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. As used herein, “identity,” or “percent identity”, with regards to an amino acid sequence, means the percentage of amino acids that are identical between two amino acid sequences when the amino acid sequences are aligned for maximal similarity. Percent identity 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). As used herein, the term “internucleoside linkage” is 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. “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. As used herein, “main chain” means a linear peptidic chain formed by the, e.g., α-amino acid amides of a polypeptide, irrespective of any loops or cyclic amino acid acids. 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 NH2moiety of a polypeptide main chain. Appending 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, “C-terminus” refers to the terminal COOH moiety of a polypeptide main chain. Appending 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, “mismatch” or “non-complementary” means a nucleobase of a first oligonucleotide that is not complementary with the corresponding nucleobase of a second oligonucleotide or target nucleic acid when the first and second oligonucleotide are aligned. 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, “natural amino acid” means Gly or theL-isomer of each of the following: Ala, Arg, Asn, Asp, Cys, Gln, Glu, His, Ile, Lys, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val. As used herein, “non-natural amino acid” means any amino acid other than the standard twenty amino acids encoded by the human genetic code, includingD-isomers of each of the following: Ala, Arg, Asn, Asp, Cys, Gln, Glu, His, Ile, Lys, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val. A non-natural amino acid may have a modified or functionalized side chain (e.g., through the attachment of a linker) Examples of non- natural amino acids include, but are not limited to, allo-isoleucine, 2-amino-3-ethyl-pentanoic acid, aminoisobutyric acid, aminobutyric acid, azetidine-2-carboxylic acid, 7-azatryptophan, 6-azidolysine, β- cyclobutylalanine, β-methyl isoleucine, 4,4-biphenylalanine, cis-hydroxyproline, cyclobutyl glycine, cyclohexyl glycine, cyclopentyl alanine, cyclopentyl glycine, 2,6-dimethyl tyrosine, 3,3-diphenyl alanine, 4- trans-hydroxy-L-proline, 1-napthylalanine, 2-napthylalanine, N-methyl alanine, 1-methyl histidine, 3-methyl histidine, N-methyl-tryptophan, pipecolic acid, 4-pyridylalanine, sarcosine, t-butyl alanine, or 3-t-butyl tyrosine. 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 pairing with at least one other nucleobase. A “5-methylcytosine” is a modified nucleobase. Inosine (I) is a nucleoside comprising the modified nucleobase hypoxanthine. 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. In certain embodiments, such modified side-chains are cysteine amino acids that either form a disulfide bond with a non-adjacent cysteine or a covalent bond with a molecular scaffold such as TATA or TATB. In certain embodiments, such modified side chains are azido- modified glutamate, or the products of a click reaction with an azido-modified glutamate. As used herein, “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, “molecular scaffold” means a chemical group that forms covalent bonds with the reactive groups of a polypeptide to form at least two polypeptide loops joined by the molecular scaffold. In certain embodiments, the molecular scaffold is 1,1’,1’’-(1,3,5-triazinane-1,3,5-triyl)triprop-2-en-1-one (TATA). In certain embodiments, the molecular scaffold is 1,1’,1’’-(1,3,5-triazinane-1,3,5-triyl)tris(2-bromoethanone) (TATB). As used herein, “oligomeric agent” means an oligomeric compound and optionally one or more additional features, such as a second oligomeric compound. An oligomeric agent may be a single-stranded oligomeric compound or may be an oligomeric duplex formed by two complementary oligomeric compounds. As used herein, “oligomeric compound” means an oligonucleotide and optionally one or more additional features, such as a terminal group or linker. An oligomeric compound may be paired with a second oligomeric compound that is complementary to the first oligomeric compound or may be unpaired. A “singled-stranded oligomeric compound” is an unpaired oligomeric compound. In certain embodiments, an oligomeric compound comprises a modified oligonucleotide and a transferrin-receptor binding moiety or a half-life extension moiety, and optionally a linker. The term “oligomeric duplex” means a duplex formed by two oligomeric compounds having complementary nucleobase sequences. As used herein, “oligonucleotide” means a strand of linked nucleosides connected via internucleoside linkages, wherein each nucleoside and internucleoside linkage independently may be modified or unmodified. Unless otherwise indicated, oligonucleotides consist of 8-50 linked nucleosides. As used herein, “modified oligonucleotide” means an oligonucleotide, wherein at least one nucleoside or internucleoside linkage is modified. As used herein, “unmodified oligonucleotide” means an oligonucleotide that does not comprise any nucleoside modifications or internucleoside modifications. The “5’-end” means the 5’-most nucleoside in an oligonucleotide. In certain embodiments, the “5’-end” means the 5’-position of the 5’-most nucleoside in an oligonucleotide. The “3’-end” means the 3’-most nucleoside in an oligonucleotide. In certain embodiments, the “3’-end” means the 3’-position of the 3’-most nucleoside in an oligonucleotide. As used herein, “peptide” means a compound or a fragment of a compound consisting of 3 or more amino acids linked together via amide bonds. As used herein, “polypeptide” means a compound or fragment of a compound consisting of 60 or more amino acids linked together via amide bonds. As used herein, “peptide sequence” or “polypeptide sequence” means the order of contiguous amino acids in a peptide or polypeptide main chain. In the case of cyclic peptides, the peptide sequence corresponds to the linear sequence of contiguous amide-bond linked amino acids, and does not describe how this linear sequence is cyclized. As used herein, “peptidomimetic” means a compound or a fragment of a compound consisting of 3 or more amino acids or amino acid mimetics linked together, wherein at least two subunits are linked by a bond that is not an amide bond. Unless otherwise indicated, peptidomimetics consist of 3-50 amino acids or amino acid mimetics. As used herein, “pharmaceutically acceptable carrier or diluent” means any substance suitable for use in administering to a subject. Certain such carriers enable pharmaceutical compositions to be formulated as, for example, tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspension, and lozenges for the oral ingestion by a subject. In certain embodiments, a pharmaceutically acceptable carrier or diluent is sterile water, distilled water for injection, sterile saline, sterile buffer solution or sterile artificial cerebrospinal fluid. As used herein “pharmaceutically acceptable salt(s)” means physiologically and pharmaceutically acceptable salt(s) of a delivery complex. 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 including a complex suitable for administering 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 a subject or cells thereof. Typically, conversion of a prodrug within the subject is facilitated by the action of an enzyme (e.g., endogenous or viral enzyme) or chemicals present in cells or tissues and / or by physiologic conditions. In certain embodiments, the first form of the prodrug is 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. In certain embodiments, a reactive group is the sulfur atom of a cysteine amino acid. As used herein, “RNAi agent” means an antisense agent that acts, at least in part, through RISC or Ago2 to modulate a target nucleic acid and / or a protein encoded by a target nucleic acid. RNAi agents include, but are not limited to double-stranded siRNA, single-stranded RNAi (ssRNAi), and microRNA, including microRNA mimics. RNAi agents may comprise conjugate groups and / or terminal groups. In certain embodiments, an RNAi agent modulates the amount and / or activity of a target nucleic acid. The term RNAi agent excludes antisense agents that act through RNase H. As used herein, “RNase H agent” means an antisense agent that acts, at least in part, through RNase H to modulate a target nucleic acid and / or protein encoded by a target nucleic acid. RNase H agents may be single-stranded or RNase H agents may be double-stranded. RNase H compounds may comprise conjugate groups and / or terminal groups. RNase H agents may modulate 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, “self-complementary” in reference to an oligonucleotide means an oligonucleotide that at least partially hybridizes to itself. As used herein, “side chain” has its ordinary meaning in the art and means a sub-structure of an amino acid appended to, e.g., a glycine substructure of an amino acid in the main chain, and attaches to, e.g., the alpha or beta carbon of the amino acid (e.g., replacing a hydrogen in the methylene of a glycine). 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. As used herein, “stabilized phosphate group” refers to a 5’-chemical moiety that results in stabilization of a 5’-phosphate moiety of the 5’-terminal nucleoside of an oligonucleotide, relative to the stability of an unmodified 5’-phosphate of an unmodified nucleoside under biologic conditions. Such stabilization of a 5’-phophate group includes but is not limited to resistance to removal by phosphatases. Stabilized phosphate groups include, but are not limited to, 5’-vinyl phosphonates and 5’-cyclopropyl phosphonate. As used herein, “stereorandom” or “stereorandom chiral center” in the context of a population of molecules of identical molecular formula means a chiral center that is not controlled during synthesis, or enriched following synthesis, for a particular absolute stereochemical configuration. The stereochemical configuration of a chiral center is random when it is the result of a synthetic method that is not designed to control the stereochemical configuration. For example, in a population of molecules comprising a stereorandom chiral center, the number of molecules having the (S) configuration of the stereorandom chiral center may be the same as the number of molecules having the (R) configuration of the stereorandom chiral center (“racemic”). In certain embodiments, the stereorandom chiral center is not 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. In certain embodiments, the stereorandom chiral center is at the phosphorous atom of a stereorandom phosphorothioate or mesyl phosphoramidate internucleoside linkage. As used herein, “subject” refers to a human or non-human animal, including, but not limited to, mice, rats, rabbits, dogs, cats, pigs, and non-human primates, including, but not limited to, monkeys and chimpanzees. 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) ribosyl moiety, as found in RNA (an “unmodified RNA sugar moiety”), or a 2’-H(H) deoxyribosyl sugar moiety, as found in DNA (an “unmodified DNA sugar moiety”). Unmodified sugar moieties have one hydrogen at each of the 1’, 3’, and 4’ positions, an oxygen at the 3’ position, and two hydrogens at the 5’ position. As used herein, “modified sugar moiety” or “modified sugar” means a modified furanosyl sugar moiety or a sugar surrogate. As used herein, "sugar surrogate" means a modified sugar moiety having other than a furanosyl moiety that can link a nucleobase to an internucleoside linkage. Modified nucleosides comprising sugar surrogates can be incorporated into one or more positions within an oligonucleotide and such oligonucleotides are capable of hybridizing to complementary oligomeric compounds or target nucleic acids. As used herein, “target nucleic acid” and “target RNA” mean a nucleic acid that an oligomeric compound is designed 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 oligomeric compound is designed to hybridize. As used herein, "terminal group" means a chemical group or group of atoms that is covalently linked to a terminus of an oligonucleotide. As used herein, “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 and / or GenBank Gene ID 7037. “Mouse transferrin receptor” and “mouse TfR1” means the protein encoded by the gene represented by ENSEMBL ID ENSMUSG00000022797 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, “antisense activity” means any detectable and / or measurable change attributable to the hybridization of an antisense compound to its target nucleic acid. In certain embodiments, antisense activity is a decrease in the amount or expression of a target nucleic acid or protein encoded by such target nucleic acid compared to target nucleic acid levels or target protein levels in the absence of the antisense compound. In certain embodiments, antisense activity is the modulation of splicing of a target pre-mRNA. As used herein, “antisense oligonucleotide” means an oligonucleotide, including the oligonucleotide portion of an antisense compound, that is capable of hybridizing to a target nucleic acid and is capable of at least one antisense activity. Antisense oligonucleotides include but are not limited to antisense RNAi oligonucleotides and antisense RNase H oligonucleotides. As used herein, “sense oligonucleotide” means an oligonucleotide, including the oligonucleotide portion of a sense compound, that is capable of hybridizing to an antisense oligonucleotide. 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, “treating” means improving a subject’s disease or condition by administering a cargo described herein. In certain embodiments, treating a subject improves a symptom relative to the same symptom in the absence of the treatment. In certain embodiments, treatment reduces in the severity or frequency of a symptom, or delays the onset of a symptom, slows the progression of a symptom, or slows the severity or frequency of a symptom. As used herein, “therapeutically effective amount” means an amount of an oligomeric agent or pharmaceutical composition that provides a therapeutic benefit to a subject. For example, a therapeutically effective amount improves a symptom of a disease. As used herein, “albumin-binding moiety” means a ligand that binds to a mammalian serum albumin, such as human serum albumin or mouse serum albumin. As used herein, a “half-life extension moiety” means a ligand that increases the half-life of a compound or complex in vivo, when compared to the same compound or complex without the ligand. A half- life extension moiety may be a protein binding moiety that binds to a serum protein, such as albumin. A half- life extension moiety may be a fatty acid or other lipophilic moiety. CERTAIN EMBODIMENTS The present disclosure provides the following non-limiting numbered embodiments: Embodiment 1. A complex, comprising at least one cargo, at least one half-life extension moiety, and at least one transferrin-receptor binding moiety; wherein the transferrin-receptor binding moiety does not comprise an scFv domain; and wherein the complex does not comprise an Fc domain. Embodiment 2. The complex of embodiment 1, wherein at least one transferrin-receptor binding moiety is covalently attached to at least one half-life extension moiety, optionally through a linker. Embodiment 3. The complex of embodiment 1 or 2, wherein at least one transferrin-receptor binding moiety is covalently attached to at least one cargo, optionally through a linker. Embodiment 4. The complex of any of embodiments 1-3, wherein at least one half-life extension moiety is covalently attached to at least one cargo, optionally through a linker. Embodiment 5. The complex of any of embodiments 1-4, comprising exactly one transferrin-receptor binding moiety. Embodiment 6. The complex of any of embodiments 1-5, wherein the transferrin-receptor binding moiety is selected from a peptide or protein. Embodiment 7. The complex of embodiment 6, wherein the transferrin-receptor binding moiety is a linear peptide, a cyclic peptide, or a bicyclic peptide. Embodiment 8. The complex of embodiment 7, wherein the transferrin-receptor binding moiety comprises a bicyclic peptide with a linear amino acid sequence having at least 80%, at least 90%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 2, 3, 21-29, or 31-191. Embodiment 9. The complex of embodiment 6, wherein the transferrin-receptor binding moiety is a VNAR or a VHH. Embodiment 10. The complex of any of embodiments 6-9, wherein the half-life extension moiety is attached at the N-terminus of the transferrin-receptor binding moiety, optionally through a linker. Embodiment 11. The complex of any of embodiments 6-9, wherein the half-life extension moiety is attached at the C-terminus of the transferrin-receptor binding moiety, optionally through a linker. Embodiment 12. The complex of any of embodiments 6-9, wherein the half-life extension moiety is attached through a side chain of the transferrin-receptor binding moiety, optionally through a linker. Embodiment 13. The complex of any of embodiments 6-12, wherein the cargo is attached at the N- terminus of the transferrin-receptor binding moiety, optionally through a linker. Embodiment 14. The complex of any of embodiments 6-12, wherein the cargo is attached at the C- terminus of the transferrin-receptor binding moiety, optionally through a linker. Embodiment 15. The complex of any of embodiments 6-12, wherein the cargo is attached through a side chain of the transferrin-receptor binding moiety, optionally through a linker. Embodiment 16. The complex of any of embodiments 1-15, comprising exactly one half-life extension moiety. Embodiment 17. The complex of any of embodiments 1-15, comprising exactly two half-life extension moieties. Embodiment 18. The complex of any of embodiments 1-17, wherein the half-life extension moiety is an albumin-binding moiety, an FcRn-binding moiety, or an IgG-binding moiety. Embodiment 19. The complex of embodiment 18, wherein the half-life extension moiety is an albumin-binding moiety. Embodiment 20. The complex of embodiment 19, wherein the albumin-binding moiety is a fatty acid. Embodiment 21. The complex of embodiment 20, wherein the albumin-binding moiety comprises: . Embodiment 22. The complex of embodiment 18, wherein the half-life extension moiety is a peptide or protein. Embodiment 23. The complex of embodiment 22, wherein the transferrin-receptor binding moiety is attached at the N-terminus of the half-life extension moiety, optionally through a linker. Embodiment 24. The complex of embodiment 22, wherein the transferrin-receptor binding moiety is attached at the C-terminus of the half-life extension moiety, optionally through a linker. Embodiment 25. The complex of embodiment 22, wherein the transferrin-receptor binding moiety is attached through a side chain of the half-life extension moiety, optionally through a linker. Embodiment 26. The complex of any of embodiments 22-25, wherein the cargo is attached at the N- terminus of the half-life extension moiety, optionally through a linker. Embodiment 27. The complex of any of embodiments 22-25, wherein the cargo is attached at the C- terminus of the half-life extension moiety, optionally through a linker. Embodiment 28. The complex of any of embodiments 22-25, wherein the cargo is attached through a side chain of half-life extension moiety, optionally through a linker. Embodiment 29. The complex of any of embodiments 22-28, wherein the half-life extension moiety is an albumin-binding peptide. Embodiment 30. The complex of embodiment 29, wherein the albumin binding peptide has a linear amino acid sequence with at least 80%, at least 90%, at least 95%, or 100% identity any of SEQ ID NOs: 4, 266, or 267. Embodiment 31. The complex of embodiment any of embodiments 18 or 22-28, wherein the half-life extension moiety is an FcRn-binding moiety. Embodiment 32. The complex of embodiment 31, wherein the FcRn-binding moiety is a peptide. Embodiment 33. The complex of embodiment 32, wherein the peptide has a linear amino acid sequence having at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 277 or 278. Embodiment 34. The complex of any of embodiments 1-33, wherein at least one linker comprises a hydrophilic moiety. Embodiment 35. The complex of embodiment 34, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine. Embodiment 36. The complex of embodiment 35, wherein at least one linker comprises a PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 37. The complex of embodiment 35, wherein at least one linker comprises (sarcosine)n, where is n is 1 to 10. Embodiment 38. The complex of any of embodiments 1-37, wherein the cargo is selected from an oligomeric agent, a small molecule, a peptide, a protein, or a fluorophore. Embodiment 39. The complex of any of embodiments 1-38, wherein the wherein the complex is represented by one of the following formulae: A‐L1‐T‐L2‐C  T‐L1‐A‐L2‐C  C‐L1‐T‐L2‐A  C‐L1‐A‐L2‐T  A‐L1‐C‐L2‐T  T‐L1‐C‐L2‐A;  wherein A represents a half-life extension moiety; T represents a transferrin-receptor binding moiety, C represents a cargo; each of L1and L2is an independently selected linker. Embodiment 40. The complex of any of embodiments 1-38, wherein the complex is represented by one of the following formulae: A—L1     B—L2—C          L1—A  C—L2—B    A represents an life extension moiety; T represents a transferrin-receptor binding moiety, C represents a cargo; each of L1, L2, and L3represents an independently selected linker; and B is a branching group. Embodiment 41. The complex of embodiment 39 or 40, wherein at least one linker comprises a hydrophilic moiety. Embodiment 42. The complex of embodiment 41, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine. Embodiment 43. The complex of any of embodiments 39-41, wherein L1comprises PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 44. The complex of any of embodiments 39-43, wherein L1comprises (sarcosine)n, where is n is 1 to 10. Embodiment 45. The complex of any of embodiments 39-44, wherein L2comprises PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 46. The complex of any of embodiments 39-44, wherein L2comprises (sarcosine)n, where is n is 1 to 10. Embodiment 47. The complex of any of embodiments 40-46, wherein L3comprises PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 48. The complex of any of embodiments 40-46, wherein L3comprises (sarcosine)n, where is n is 1 to 10. Embodiment 49. The complex of any of embodiments 40-48, wherein B is a branching group selected . of any of embodiments 39-49, wherein the transferrin-receptor binding a or protein. Embodiment 51. The complex of embodiment 50, wherein the transferrin-receptor binding moiety is a linear peptide, a cyclic peptide, or a bicyclic peptide. Embodiment 52. The complex of embodiment 51, wherein the transferrin-receptor binding moiety is a bicyclic peptide with a linear amino acid sequence having at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 2, 3, 21-29, or 31-191. Embodiment 53. The complex of embodiment 51, wherein the transferrin-receptor binding moiety is a VNAR or a VHH. Embodiment 54. The complex of any of embodiments 39-53, wherein the half-life extension moiety is an albumin-binding moiety, an FcRn-binding moiety, or an IgG-binding moiety. Embodiment 55. The complex of embodiment 54, wherein the half-life extension moiety is an albumin-binding moiety. Embodiment 56. The complex of embodiment 55, wherein the albumin-binding moiety is a fatty acid. Embodiment 57. The complex of embodiment 56, wherein the albumin-binding moiety comprises: . Embodiment 59. The complex of embodiment 55, wherein the peptide has a linear amino acid sequence with at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 4, 266, or 267. Embodiment 60. The complex of embodiment 54, wherein the half-life extension moiety is an FcRn- binding moiety. Embodiment 61. The complex of embodiment 60, wherein the FcRn-binding moiety is a peptide. Embodiment 62. The complex of embodiment 60, wherein the peptide has a linear amino acid sequence having at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 277 or 278. Embodiment 63. The complex of any of embodiments 1-62, wherein the complex consists of a cargo and the structure: , wherein n is 10-30. Embodiment 64. The complex of any of embodiments 1-63, wherein the transferrin receptor binding moiety has a molecular weight that is less than 15 kD, less than 14 kD, less than 13 kD, less than 12 kD, less than 11 kD, less than 10 kD, less than 9 kD, less than 8 kD, less than 7 kD, less than 6 kD, less than 5 kD, less than 4 kD, less than 3 kD, less than 2 kD, less than 1.5 kD, or less than 1 kD. Embodiment 65. The complex of embodiment 64, wherein the transferrin receptor binding moiety is a protein with a molecular weight of 12 kD-15 kD. Embodiment 66. The complex of embodiment 64, wherein the transferrin receptor binding moiety is a peptide with a molecular weight of 500 Da-1 kD, 500 Da-1.5 kD, 500 Da-2 kD, 1 kD-2 kD, 1 kD-1.5 kD, or 1.5 kD-2 kD. Embodiment 67. The complex of embodiment 64, wherein the transferrin receptor binding moiety is a protein comprising 105-140 amino acids. Embodiment 68. The complex of embodiment 64, wherein the transferrin receptor binding moiety is a peptide consisting of 8-22, 10-22, 10-20, 10-18, 10-16, 12-16, 12-18, 12-20, 12-22, 14-22, 14-16, 14- 18, 14-20, 16-20 linked amino acids. Embodiment 69. The complex of any of embodiments 1-68, wherein the half-life extension moiety has a molecular weight that is less than 15 kD, less than 14 kD, less than 13 kD, less than 12 kD, less than 11 kD, less than 10 kD, less than 9 kD, less than 8 kD, less than 7 kD, less than 6 kD, less than 5 kD, less than 4 kD, less than 3 kD, less than 2 kD, less than 1.5 kD, less 1000 kDa, less than 900 kDa, less than 800 kDa, less than 700 kDa, less than 600 kDa, less than 500 kDa, less than 400 kDa, or less than 300 kDa. Embodiment 70. The complex of embodiment 69, wherein the half-life extension moiety is a protein with a molecular weight of 12 kD-15 kD Embodiment 71. The complex of embodiment 69, wherein the half-life extension moiety is a peptide with a molecular weight of 500 Da-1 kD, 500 Da-1.5 kD, 500 Da-2 kD, 1 kD-2 kD, 1 kD-1.5 kD, or 1.5 kD-2 kD. Embodiment 72. The complex of embodiment 69, wherein the albumin binding moiety is a protein comprising 105-140 amino acids. Embodiment 73. The complex of embodiment 69, wherein the half-life extension moiety is a peptide consisting of 8-22, 10-22, 10-20, 10-18, 10-16, 12-16, 12-18, 12-20, 12-22, 14-22, 14-16, 14-18, 14- 20, 16-20 linked amino acids. Embodiment 74. The complex of embodiment 69, wherein the half-life extension moiety comprises a fatty acid and has a molecular weight of less than 1000 kDa, less than 900 kDa, less than 800 kDa, less than 700 kDa, less than 600 kDa, less than 500 kDa, less than 400 kDa, or less than 300 kDa. Embodiment 75. The complex of any of embodiments 39-63, wherein the combined molecular weight of A+T+L1+L2+L3+B is less than 50 kD, less than 45 kD, less than 40 kD, less than 35 kD, less than 30 kD, less than 25 kD, less than 20 kD, less than 15 kD, less than 10 kD, less than 5 kD, less than 4 kD, less than 3 kD, or less than 2 kD. Embodiment 76. The complex of any of embodiments 1-75, wherein the cargo is an oligomeric agent comprising at least a first modified oligonucleotide consisting of 12-80 linked nucleosides. Embodiment 77. The complex of embodiment 76, wherein the transferrin-receptor binding moiety is attached at the 3’-end of the first modified oligonucleotide, optionally through a first linker. Embodiment 78. The complex of embodiment 76, wherein the transferrin-receptor binding moiety is attached at the 5’-end of the first modified oligonucleotide, optionally through a first linker. Embodiment 79. The complex of embodiment 76, wherein the transferrin-receptor binding moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a first linker. Embodiment 80. The complex of any of embodiments 76-79, wherein the half-life extension moiety is attached at the 3’-end of the first modified oligonucleotide, optionally through a second linker. Embodiment 81. The complex of any of embodiments 76-79, wherein half-life extension moiety is attached at the 5’-end of the first modified oligonucleotide, optionally through a second linker. Embodiment 82. The complex of any of embodiments 76-79, wherein the half-life extension moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a second linker. Embodiment 83. The complex of any of embodiments 76-82, wherein the half-life extension moiety is attached to the transferrin-receptor binding moiety, optionally through a linker. Embodiment 84. The complex of embodiment 76, wherein the complex comprises a branching group, wherein the transferrin-receptor binding moiety is attached to the branching group, optionally through a first linker, the half-life extension moiety is attached to the branching group, optionally through a second linker. Embodiment 85. The complex of embodiment 84, wherein the branching group is attached at the 3’- end of the first modified oligonucleotide, optionally through a third linker. Embodiment 86. The complex of embodiment 84, wherein the branching group is attached at the 5’- end of the first modified oligonucleotide, optionally through a third linker. Embodiment 87. The complex of embodiment 84, wherein the branching group is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a third linker. Embodiment 88. The complex of any of embodiments 76-87, comprising at least one linker. Embodiment 89. The complex of embodiment 88, wherein at least one linker comprises a hydrophilic moiety. Embodiment 90. The complex of embodiment 89, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine. Embodiment 91. The complex of embodiment 90, wherein at least one linker comprises PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 92. The complex of embodiment 90, wherein at least one linker comprises (sarcosine)n, where is n is 1 to 10. Embodiment 93. The complex of any of embodiments 84-92, wherein the branching group is selected . of any of embodiments 76-83 or 88-92, wherein the transferrin receptor binding moiety and the half-life extension moiety are attached at different ends of the modified oligonucleotide. Embodiment 95. The complex of embodiment 76, comprising a compound that is represented by one of the following formulae:  A‐L1‐T‐L2‐X  T‐L1‐A‐L2‐X  X‐L1‐T‐L2‐A  X‐L1‐A‐L2‐T  A‐L1‐X‐L2‐T  T‐L1‐X‐L2‐A  A—L1     B—L2—X          L1—A  X—L2—B    life extension moiety; T represents a transferrin-receptor binding moiety, X represents a modified oligonucleotide (from 5’ to 3’); each of L1, L2and L3represent an independently selected linker; and B is a branching group. Embodiment 96. The complex of embodiment 95, wherein at least one linker comprises a hydrophilic moiety. Embodiment 97. The complex of embodiment 96, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine. Embodiment 98. The complex of any of embodiments 95-97, wherein L1comprises PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 99. The complex of any of embodiments 95-97, wherein L1comprises (sarcosine)n, where is n is 1 to 10. Embodiment 100. The complex of any of embodiments 95-99, wherein L2comprises PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 101. The complex of any of embodiments 95-99, wherein L2comprises (sarcosine)n, where is n is 1 to 10. Embodiment 102. The complex of any of embodiments 95-101, wherein the compound comprises a branching group, and wherein L3comprises PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 103. The complex of any of embodiments 95-101, wherein the compound comprises a branching group, and wherein L3comprises (sarcosine)n, where is n is 1 to 10. Embodiment 104. The complex of any of embodiments 102-103, wherein B is a branching group selected from: and . Embodiment 105. of embodiments 95-104, wherein the transferrin-receptor binding or protein. Embodiment 106. The complex of embodiment 105, wherein the transferrin-receptor binding moiety is a linear peptide, a cyclic peptide, or a bicyclic peptide. Embodiment 107. The complex of embodiment 106, wherein the transferrin-receptor binding moiety is a bicyclic peptide with a linear amino acid sequence having at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 2, 3, 21-29, or 31-191. Embodiment 108. The complex of embodiment 105, wherein the transferrin-receptor binding moiety is a VNAR or a VHH. Embodiment 109. The complex of any of embodiments 95-108, wherein the half-life extension moiety is an albumin-binding moiety, an FcRn-binding moiety, or an IgG-binding moiety. Embodiment 110. The complex of embodiment 109, wherein the half-life extension moiety is an albumin-binding moiety. Embodiment 111. The complex of embodiment 110, wherein the albumin-binding moiety is a peptide. Embodiment 112. The complex of embodiment 111, wherein the peptide has a linear amino acid sequence with at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 4, 266-267. Embodiment 113. The complex of embodiment 110, wherein the albumin-binding moiety comprises a fatty acid. Embodiment 114. The complex of embodiment 113, wherein the albumin-binding moiety comprises . FcRn- binding moiety. Embodiment 116. The complex of embodiment 115, wherein the FcRn-binding moiety is a peptide. Embodiment 117. The complex of embodiment 116, wherein the peptide has a linear amino acid sequence having at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 277 or 278. Embodiment 118. The complex of embodiment 97, wherein L1is sarcosine, and n is from 1 to 10. Embodiment 119. The complex of any of embodiments 95-97, wherein L2is PEG and n is from 10 to 30. Embodiment 120. The complex of any of embodiments 95-97, wherein L2is sarcosine, and n is from 1 to 10. Embodiment 121. The complex of any of embodiments 76-120, wherein the oligomeric agent is single- stranded. Embodiment 122. The complex of embodiment 121, wherein the oligomeric agent is an RNAse H agent or a splicing agent. Embodiment 123. The complex of any of embodiments 76-120, wherein the oligomeric agent comprises a second modified oligonucleotide consisting of 12-80 linked nucleosides, 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 124. The complex of embodiment 123, wherein the transferrin-receptor binding moiety is attached at the 3’-end of the second modified oligonucleotide, optionally through a first linker. Embodiment 125. The complex of embodiment 123, wherein the transferrin-receptor binding moiety is attached at the 5’-end of the second modified oligonucleotide, optionally through a first linker. Embodiment 126. The complex of any of embodiments 123-125, wherein the transferrin-receptor binding moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the second modified oligonucleotide, optionally through a first linker. Embodiment 127. The complex of any of embodiments 123-126, wherein half-life extension moiety is attached at the 3’-end of the second modified oligonucleotide, optionally through a second linker. Embodiment 128. The complex of any of embodiments 123-126, wherein half-life extension moiety is attached at the 5’-end of the second modified oligonucleotide, optionally through a second linker. Embodiment 129. The complex of any of embodiments 123-126, wherein the half-life extension moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the second modified oligonucleotide, optionally through a second linker. Embodiment 130. The complex of any of embodiments 123 or 127-129, wherein the transferrin- receptor binding moiety is attached at the 3’-end of the first modified oligonucleotide, optionally through a first linker. Embodiment 131. The complex of any of embodiments 123 or 127-129, wherein the transferrin- receptor binding moiety is attached at the 5’-end of the first modified oligonucleotide, optionally through a first linker. Embodiment 132. The complex of any of embodiments 123 or 127-129, wherein the transferrin- receptor binding moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a first linker. Embodiment 133. The complex of any of embodiments 123-129, wherein the half-life extension moiety is attached at the 3’-end of the first modified oligonucleotide, optionally through a second linker. Embodiment 134. The complex of any of embodiments 123-129, wherein the half-life extension moiety is attached at the 5’-end of the first modified oligonucleotide, optionally through a second linker. Embodiment 135. The complex of any of embodiments 123-129, wherein the half-life extension moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a second linker. Embodiment 136. The complex of embodiment 123, wherein the transferrin-receptor binding moiety and the half-life extension moiety are attached to the same modified oligonucleotide. Embodiment 137. The complex of embodiment 123, wherein the transferrin-receptor binding moiety is attached to the first modified oligonucleotide and the half-life extension moiety is attached to the second modified oligonucleotide. Embodiment 138. The complex of embodiment 123, wherein the transferrin-receptor binding moiety is attached to the second modified oligonucleotide and the half-life extension moiety is attached to the first modified oligonucleotide. Embodiment 139. The complex of embodiment 123, wherein the complex comprises a branching group, wherein the transferrin-receptor binding moiety is attached to the branching group, optionally through a first linker, and wherein the half-life extension moiety is attached to the branching group, optionally through a second linker. Embodiment 140. The complex of embodiment 139, wherein the branching group is attached at the 3’- end of the first modified oligonucleotide, optionally through a third linker. Embodiment 141. The complex of embodiment 139, wherein the branching group is attached at the 5’- end of the first modified oligonucleotide, optionally through a third linker. Embodiment 142. The complex of embodiment 139, wherein the branching group is attached at the 3’- end of the second modified oligonucleotide, optionally through a third linker. Embodiment 143. The complex of embodiment 139, wherein the branching group is attached at the 5’- end of the second modified oligonucleotide, optionally through a third linker. Embodiment 144. The complex of Embodiment 145. The complex of any of embodiments 123-143, wherein the pair of modified oligonucleotides is represented by one set of the following formulae: A‐L1‐X and T‐L2‐Y;  A‐L1‐X and Y‐L2‐T;  T‐L1‐X and A‐L2‐Y;  T‐L1‐X and Y‐L2‐T;  X‐L1‐A and T‐L2‐Y;  X‐L1‐T and A‐L2‐Y;  X‐L1‐T and Y‐L2‐A;  X‐L1‐A and Y‐L2‐T;  wherein A represents an albumin-binding moiety; T represents a transferrin-receptor binding moiety, X represents a first modified oligonucleotide, Y represents a second modified oligonucleotide; and each of L1and L2is an independently selected linker. Embodiment 146. The complex of any of embodiments 123-144, 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. Embodiment 147. The complex of any of embodiments 76-145, wherein the first modified oligonucleotide comprises at least one nucleoside comprising a modified sugar moiety. Embodiment 148. The complex of embodiment 146, wherein the first modified oligonucleotide comprises at least one nucleoside comprising a non-bicyclic modified sugar moiety. Embodiment 149. The complex of embodiment 147, wherein the non-bicyclic modified sugar moiety a 2’-OMe sugar moiety, a 2’-MOE sugar moiety, a 2’-F sugar moiety, or a 2’-NMA sugar moiety. Embodiment 150. The complex of any of embodiments 146-148, wherein the first modified oligonucleotide comprises at least one nucleoside comprising a bicyclic sugar moiety. Embodiment 151. The complex of embodiment 149, wherein the bicyclic sugar moiety comprises a 4’- 2’ bridge selected from 4'-CH2-O-2' and 4'-CH(CH3)-O-2'. Embodiment 152. The complex of any of embodiments 123-150, wherein the second modified oligonucleotide comprises at least one nucleoside comprising a modified sugar moiety. Embodiment 153. The complex of embodiment 150, wherein the second modified oligonucleotide comprises at least one nucleoside comprising a non-bicyclic modified sugar moiety. Embodiment 154. The complex of embodiment 151, wherein the non-bicyclic modified sugar moiety a 2’-OMe sugar moiety, a 2’-MOE sugar moiety, a 2’-F sugar moiety, or a 2’-NMA sugar moiety. Embodiment 155. The complex of any of embodiments 123-153, wherein the second modified oligonucleotide comprises at least one nucleoside comprising a bicyclic sugar moiety. Embodiment 156. The complex of embodiment 154, wherein the bicyclic sugar moiety comprises a 4’- 2’ bridge selected from 4'-CH2-O-2' and 4'-CH(CH3)-O-2'. Embodiment 157. The complex of any of embodiments 76-155, wherein the first modified oligonucleotide comprises at least one modified internucleoside linkage. Embodiment 158. The complex of embodiment 156, wherein at least one internucleoside linkage of the first modified oligonucleotide is a phosphodiester linkage. Embodiment 159. The complex of embodiment 156, wherein at least one internucleoside linkage of the first modified oligonucleotide is a mesyl phosphoramidate internucleoside linkage. Embodiment 160. The complex of any of embodiments 156-158, wherein each internucleoside linkage of the first modified oligonucleotide is independently selected from a phosphodiester internucleoside linkage, a phosphorothioate internucleoside linkage, and a mesyl phosphoramidate internucleoside linkage. Embodiment 161. The complex of any of embodiments 123-159, wherein the second modified oligonucleotide comprises at least one modified internucleoside linkage. Embodiment 162. The complex of embodiment 160, wherein at least one internucleoside linkage of the second modified oligonucleotide is a phosphodiester linkage. Embodiment 163. The complex of embodiment 160, wherein at least one internucleoside linkage of the second modified oligonucleotide is a mesyl phosphoramidate internucleoside linkage. Embodiment 164. The complex of any of embodiments 160-162, wherein each internucleoside linkage of the second modified oligonucleotide is independently selected from a phosphodiester internucleoside linkage, a phosphorothioate internucleoside linkage, and a mesyl phosphoramidate internucleoside linkage. Embodiment 165. The complex of any of embodiments 76-163, wherein the first modified oligonucleotide consists of 12 to 20, 12 to 25, 13 to 20, 13 to 25, 14 to 20, 14 to 25, 15 to 20, 15 to 25, 16 to 18, 16 to 20, 16 to 25, 17 to 20, 17 to 25, 18 to 20, 18 to 25, 19 to 20, 19 to 25, 20 to 25, 20 to 3021-23, 21 to 25, 22 to 25, 23 to 25, 23 to 30, 18, 20, 21, or 23 linked nucleosides. Embodiment 166. The complex of any of embodiments 123-164, wherein the second modified oligonucleotide consists of 12 to 20, 12 to 25, 13 to 20, 13 to 25, 14 to 20, 14 to 25, 15 to 20, 15 to 25, 16 to 18, 16 to 20, 16 to 25, 17 to 20, 17 to 25, 18 to 20, 18 to 25, 19 to 20, 19 to 25, 20 to 25, 20 to 3021-23, 21 to 25, 22 to 25, 23 to 25, 23 to 30, 18, 20, 21, or 23 linked nucleosides. Embodiment 167. The complex of any of embodiments 123-165, wherein the oligomeric agent is an RNAi agent. Embodiment 168. The complex of any of embodiments 76-166, wherein the complex has a total molecular weight of less than 50 kD, less than 40 kD, less than 30 kD, less than 20 kD, or less than 10 kD. Embodiment 169. A method of modulating the expression of a target nucleic acid in the CNS, comprising administering a complex of any of embodiments 76-168 to a subject. Embodiment 170. The method of embodiment 168, wherein the complex is administered systemically. ADDITIONAL EMBODIMENTS Embodiment 1. A complex, comprising at least one cargo, at least one half-life extension moiety, and at least one transferrin-receptor binding moiety; wherein the transferrin-receptor binding moiety does not comprise an scFv domain; and wherein the complex does not comprise an Fc domain. Embodiment 2. The complex of embodiment 1, wherein at least one transferrin-receptor binding moiety is covalently attached to at least one half-life extension moiety, optionally through a linker. Embodiment 3. The complex of embodiment 1 or 2, wherein at least one transferrin-receptor binding moiety is covalently attached to at least one cargo, optionally through a linker. Embodiment 4. The complex of any of embodiments 1-3, wherein at least one half-life extension moiety is covalently attached to at least one cargo, optionally through a linker. Embodiment 5. The complex of any of embodiments 1-4, comprising exactly one transferrin-receptor binding moiety. Embodiment 6. The complex of any of embodiments 1-5, wherein the transferrin-receptor binding moiety is selected from a peptide or protein. Embodiment 7. The complex of embodiment 6, wherein the transferrin-receptor binding moiety is a linear peptide, a cyclic peptide, or a bicyclic peptide. Embodiment 8. The complex of embodiment 7, wherein the transferrin-receptor binding moiety comprises a bicyclic peptide with a linear amino acid sequence having at least 80%, at least 90%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 2, 3, 21-29, or 31-191. Embodiment 9. The complex of embodiment 6, wherein the transferrin-receptor binding moiety is a VNAR or a VHH. Embodiment 10. The complex of any of embodiments 6-9, wherein the half-life extension moiety is attached at the N-terminus of the transferrin-receptor binding moiety, optionally through a linker. Embodiment 11. The complex of any of embodiments 6-9, wherein the half-life extension moiety is attached at the C-terminus of the transferrin-receptor binding moiety, optionally through a linker. Embodiment 12. The complex of any of embodiments 6-9, wherein the half-life extension moiety is attached through a side chain of the transferrin-receptor binding moiety, optionally through a linker. Embodiment 13. The complex of any of embodiments 6-12, wherein the cargo is attached at the N- terminus of the transferrin-receptor binding moiety, optionally through a linker. Embodiment 14. The complex of any of embodiments 6-12, wherein the cargo is attached at the C- terminus of the transferrin-receptor binding moiety, optionally through a linker. Embodiment 15. The complex of any of embodiments 6-12, wherein the cargo is attached through a side chain of the transferrin-receptor binding moiety, optionally through a linker. Embodiment 16. The complex of any of embodiments 1-15, comprising exactly one half-life extension moiety. Embodiment 17. The complex of any of embodiments 1-15, comprising exactly two half-life extension moieties. Embodiment 18. The complex of any of embodiments 1-17, wherein the half-life extension moiety is an albumin-binding moiety, an FcRn-binding moiety, or an IgG-binding moiety. Embodiment 19. The complex of embodiment 18, wherein the half-life extension moiety is an albumin-binding moiety. Embodiment 20. The complex of embodiment 19, wherein the albumin-binding moiety is a fatty acid. Embodiment 21. The complex of embodiment 20, wherein the albumin-binding moiety comprises: . or protein. Embodiment 23. The complex of embodiment 22, wherein the transferrin-receptor binding moiety is attached at the N-terminus of the half-life extension moiety, optionally through a linker. Embodiment 24. The complex of embodiment 22, wherein the transferrin-receptor binding moiety is attached at the C-terminus of the half-life extension moiety, optionally through a linker. Embodiment 25. The complex of embodiment 22, wherein the transferrin-receptor binding moiety is attached through a side chain of the half-life extension moiety, optionally through a linker. Embodiment 26. The complex of any of embodiments 22-25, wherein the cargo is attached at the N- terminus of the half-life extension moiety, optionally through a linker. Embodiment 27. The complex of any of embodiments 22-25, wherein the cargo is attached at the C- terminus of the half-life extension moiety, optionally through a linker. Embodiment 28. The complex of any of embodiments 22-25, wherein the cargo is attached through a side chain of half-life extension moiety, optionally through a linker. Embodiment 29. The complex of any of embodiments 22-28, wherein the half-life extension moiety is an albumin-binding peptide. Embodiment 30. The complex of embodiment 29, wherein the albumin binding peptide has a linear amino acid sequence with at least 80%, at least 90%, at least 95%, or 100% identity any of SEQ ID NOs: 4, 266, or 267. Embodiment 31. The complex of embodiment any of embodiments 18 or 22-28, wherein the half-life extension moiety is an FcRn-binding moiety. Embodiment 32. The complex of embodiment 31, wherein the FcRn-binding moiety is a peptide. Embodiment 33. The complex of embodiment 32, wherein the peptide has a linear amino acid sequence having at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 277 or 278. Embodiment 34. The complex of any of embodiments 1-33, wherein at least one linker comprises a hydrophilic moiety. Embodiment 35. The complex of embodiment 34, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine. Embodiment 36. The complex of embodiment 35, wherein at least one linker comprises a PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 37. The complex of embodiment 35, wherein at least one linker comprises (sarcosine)n, where is n is 1 to 10. Embodiment 38. The complex of any of embodiments 1-37, wherein the cargo is selected from an oligomeric agent, a small molecule, a peptide, a protein, or a fluorophore. Embodiment 39. The complex of any of embodiments 1-38, wherein the wherein the complex is represented by one of the following formulae: A‐L1‐T‐L2‐C  T‐L1‐A‐L2‐C  C‐L1‐T‐L2‐A  C‐L1‐A‐L2‐T  A‐L1‐C‐L2‐T  T‐L1‐C‐L2‐A;  wherein A represents a half-life extension moiety; T represents a transferrin-receptor binding moiety, C represents a cargo; each of L1and L2is an independently selected linker. Embodiment 40. The complex of any of embodiments 1-38, wherein the complex is represented by one of the following formulae: A—L1     B—L2—C        T—L3       L1—A  wherein A represents an half-life extension moiety; T represents a transferrin-receptor binding moiety, C represents a cargo; each of L1, L2, and L3represents an independently selected linker; and B is a branching group. Embodiment 41. The complex of embodiment 39 or 40, wherein at least one linker comprises a hydrophilic moiety. Embodiment 42. The complex of embodiment 41, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine. Embodiment 43. The complex of any of embodiments 39-41, wherein L1comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 44. The complex of any of embodiments 39-43, wherein L1comprises (sarcosine)n, where is n is 1 to 10. Embodiment 45. The complex of any of embodiments 39-44, wherein L2comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 46. The complex of any of embodiments 39-44, wherein L2comprises (sarcosine)n, where is n is 1 to 10. Embodiment 47. The complex of any of embodiments 40-46, wherein L3comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 48. The complex of any of embodiments 40-46, wherein L3comprises (sarcosine)n, where is n is 1 to 10. Embodiment 49. The complex of any of embodiments 40-48, wherein B is a branching group selected . of any of embodiments 39-49, wherein the transferrin-receptor binding moiety is a peptide or a protein. Embodiment 51. The complex of embodiment 50, wherein the transferrin-receptor binding moiety is a linear peptide, a cyclic peptide, or a bicyclic peptide. Embodiment 52. The complex of embodiment 51, wherein the transferrin-receptor binding moiety is a bicyclic peptide with a linear amino acid sequence having at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 2, 3, 21-29, or 31-191. Embodiment 53. The complex of embodiment 51, wherein the transferrin-receptor binding moiety is a VNAR or a VHH. Embodiment 54. The complex of any of embodiments 39-53, wherein the half-life extension moiety is an albumin-binding moiety, an FcRn-binding moiety, or an IgG-binding moiety. Embodiment 55. The complex of embodiment 54, wherein the half-life extension moiety is an albumin-binding moiety. Embodiment 56. The complex of embodiment 55, wherein the albumin-binding moiety is a fatty acid. Embodiment 57. The complex of embodiment 56, wherein the albumin-binding moiety comprises: . Embodiment 59. The complex of embodiment 55, wherein the peptide has a linear amino acid sequence with at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 4, 266, or 267. Embodiment 60. The complex of embodiment 54, wherein the half-life extension moiety is an FcRn- binding moiety. Embodiment 61. The complex of embodiment 60, wherein the FcRn-binding moiety is a peptide. Embodiment 62. The complex of embodiment 60, wherein the peptide has a linear amino acid sequence having at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 277 or 278. Embodiment 63. The complex of any of embodiments 1-62, wherein the complex consists of a cargo and the structure:

[0002] , wherein n is 10-30. Embodiment 64. The complex of embodiment 30, wherein the albumin binding peptide is SA21 (SEQ ID NO.: 266) or ABDCon (SEQ ID NO.: 267). Embodiment 65. The complex of embodiment 64, wherein the half-life extension moiety is attached through a linker. Embodiment 66. The complex of embodiment 65, wherein the linker comprises an N-terminal G[Ac- K-heterocyclyl], wherein [Ac-K- . Embodiment 67. The complex of moiety is  or Em through a linker. Embodiment 69. The complex of embodiment 68, wherein the linker comprises a hydrophilic moiety. Embodiment 70. The complex of embodiment 69, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine. Embodiment 71. The complex of embodiment 70, wherein the linker comprises a PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 72. The complex of embodiment 71, wherein the linker comprises . of embodiment 71 or 72, wherein the linker is . transferrin receptor binding moiety has a molecular weight that is less than 15 kD, less than 14 kD, less than 13 kD, less than 12 kD, less than 11 kD, less than 10 kD, less than 9 kD, less than 8 kD, less than 7 kD, less than 6 kD, less than 5 kD, less than 4 kD, less than 3 kD, less than 2 kD, less than 1.5 kD, or less than 1 kD. Embodiment 76. The complex of embodiment 75, wherein the transferrin receptor binding moiety is a protein with a molecular weight of 12 kD-15 kD. Embodiment 77. The complex of embodiment 64, wherein the transferrin receptor binding moiety is a peptide with a molecular weight of 500 Da-1 kD, 500 Da-1.5 kD, 500 Da-2 kD, 1 kD-2 kD, 1 kD-1.5 kD, or 1.5 kD-2 kD. Embodiment 78. The complex of embodiment 77, wherein the transferrin receptor binding moiety is a bicyclic peptide having a total molecular weight including scaffold of 500 Da-1 kD, 500 Da-1.5 kD, 500 Da-2 kD, 1 kD-2 kD, 1 kD-1.5 kD, or 1.5 kD-2 kD. Embodiment 79. The complex of embodiment 75, wherein the transferrin receptor binding moiety is a protein comprising 105-140 amino acids. Embodiment 80. The complex of embodiment 75, wherein the transferrin receptor binding moiety is a peptide comprising or consisting of 8-22, 10-22, 10-20, 10-18, 10-16, 12-16, 12-18, 12-20, 12-22, 14- 22, 14-16, 14-18, 14-20, 16-20 linked amino acids. Embodiment 81. The complex of any of embodiments 1-80, wherein the half-life extension moiety has a molecular weight that is less than 15 kD, less than 14 kD, less than 13 kD, less than 12 kD, less than 11 kD, less than 10 kD, less than 9 kD, less than 8 kD, less than 7 kD, less than 6 kD, less than 5 kD, less than 4 kD, less than 3 kD, less than 2 kD, less than 1.5 kD, less 1000 kDa, less than 900 kDa, less than 800 kDa, less than 700 kDa, less than 600 kDa, less than 500 kDa, less than 400 kDa, or less than 300 kDa. Embodiment 82. The complex of embodiment 81, wherein the half-life extension moiety is a protein with a molecular weight of 12 kD-15 kD. Embodiment 83. The complex of embodiment 81, wherein the half-life extension moiety is a peptide with a molecular weight of 500 Da-1 kD, 500 Da-1.5 kD, 500 Da-2 kD, 1 kD-2 kD, 1 kD-1.5 kD, or 1.5 kD-2 kD. Embodiment 84. The complex of embodiment 81, wherein the albumin binding moiety is a protein comprising 105-140 amino acids. Embodiment 85. The complex of embodiment 81, wherein the half-life extension moiety is a peptide consisting of 8-22, 10-22, 10-20, 10-18, 10-16, 12-16, 12-18, 12-20, 12-22, 14-22, 14-16, 14-18, 14- 20, 16-20 linked amino acids. Embodiment 86. The complex of embodiment 81, wherein the half-life extension moiety comprises a fatty acid and has a molecular weight of less than 1000 kDa, less than 900 kDa, less than 800 kDa, less than 700 kDa, less than 600 kDa, less than 500 kDa, less than 400 kDa, or less than 300 kDa. Embodiment 87. The complex of any of embodiments 39-63, wherein the combined molecular weight of A+T+L1+L2+L3+B is less than 50 kD, less than 45 kD, less than 40 kD, less than 35 kD, less than 30 kD, less than 25 kD, less than 20 kD, less than 15 kD, less than 10 kD, less than 5 kD, less than 4 kD, less than 3 kD, or less than 2 kD. Embodiment 88. The complex of any of embodiments 1-87, wherein the cargo is an oligomeric agent comprising at least a first modified oligonucleotide consisting of 12-80 linked nucleosides. Embodiment 89. The complex of embodiment 88, wherein the transferrin-receptor binding moiety is attached at the 3’-end of the first modified oligonucleotide, optionally through a first linker. Embodiment 90. The complex of embodiment 88, wherein the transferrin-receptor binding moiety is attached at the 5’-end of the first modified oligonucleotide, optionally through a first linker. Embodiment 91. The complex of any of embodiments 88-90, wherein the transferrin-receptor binding moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a first linker. Embodiment 92. The complex of embodiment 91, wherein the transferrin-receptor binding moiety is attached at the 2’-position of a modified sugar moiety. Embodiment 93. The complex of any of embodiments 88-91, wherein the half-life extension moiety is attached at the 3’-end of the first modified oligonucleotide, optionally through a second linker. Embodiment 94. The complex of any of embodiments 88-91, wherein half-life extension moiety is attached at the 5’-end of the first modified oligonucleotide, optionally through a second linker. Embodiment 95. The complex of any of embodiments 88-94, wherein the half-life extension moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a second linker. Embodiment 96. The complex of embodiment 95, wherein the half-life extension moiety is attached at the 2’-position of a modified sugar moiety. Embodiment 97. The complex of any of embodiments 88-96, wherein the half-life extension moiety is attached to the transferrin-receptor binding moiety, optionally through a linker. Embodiment 98. The complex of embodiment 88, wherein the complex comprises a branching group, wherein the transferrin-receptor binding moiety is attached to the branching group, optionally through a first linker, the half-life extension moiety is attached to the branching group, optionally through a second linker. Embodiment 99. The complex of embodiment 98, wherein the branching group is attached at the 3’- end of the first modified oligonucleotide, optionally through a third linker. Embodiment 100. The complex of embodiment 98, wherein the branching group is attached at the 5’- end of the first modified oligonucleotide, optionally through a third linker. Embodiment 101. The complex of any of embodiments 98-100, wherein the branching group is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a third linker. Embodiment 102. The complex of any of embodiments 98-101, wherein the branching group is selected from: and . Embodiment 103. of embodiments 88-101, comprising at least one linker. Embodiment 104. 102, wherein at least one linker comprises a hydrophilic moiety. Embodiment 105. The complex of embodiment 103, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine. Embodiment 106. The complex of embodiment 104, wherein at least one linker comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 107. The complex of embodiment 104, wherein at least one linker comprises (sarcosine)n, where is n is 1 to 10. Embodiment 108. The complex of any of embodiments 88-97 or 103-107, wherein the transferrin receptor binding moiety and the half-life extension moiety are attached at different positions of the modified oligonucleotide. Embodiment 109. The complex of embodiment 88, comprising a compound that is represented by one of the following formulae:  A‐L1‐T‐L2‐X  T‐L1‐A‐L2‐X  X‐L1‐T‐L2‐A  X‐L1‐A‐L2‐T  A‐L1‐X‐L2‐T  T‐L1‐X‐L2‐A  A—L1       L1—A  wherein A represents an half-life extension moiety; T represents a transferrin-receptor binding moiety, X represents a modified oligonucleotide (from 5’ to 3’); each of L1, L2and L3represent an independently selected linker; and B is a branching group. Embodiment 110. The complex of embodiment 109, wherein at least one linker comprises a hydrophilic moiety. Embodiment 111. The complex of embodiment 110, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine. Embodiment 112. The complex of any of embodiments 109-111, wherein L1comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 113. The complex of any of embodiments 109-112, wherein L1comprises (sarcosine)n, where is n is 1 to 10. Embodiment 114. The complex of any of embodiments 109-113, wherein L2comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 115. The complex of any of embodiments 109-114, wherein L2comprises (sarcosine)n, where is n is 1 to 10. Embodiment 116. The complex of any of embodiments 109-115, wherein the compound comprises a branching group B, and wherein L3comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24. Embodiment 117. The complex of any of embodiments 109-116, wherein the compound comprises a branching group B, and wherein L3comprises (sarcosine)n, where is n is 1 to 10. Embodiment 118. The complex of any of embodiments 109-117, wherein B is a branching group selected from: . Embodiment 119. of embodiments 109-118, wherein the transferrin-receptor binding moiety is selected from a peptide or protein. Embodiment 120. The complex of embodiment 119, wherein the transferrin-receptor binding moiety is a linear peptide, a cyclic peptide, or a bicyclic peptide. Embodiment 121. The complex of embodiment 120, wherein the transferrin-receptor binding moiety is a bicyclic peptide with a linear amino acid sequence having at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 2, 3, 21-29, or 31-191. Embodiment 122. The complex of embodiment 119, wherein the transferrin-receptor binding moiety is a VNAR or a VHH. Embodiment 123. The complex of any of embodiments 109-122, wherein the half-life extension moiety is an albumin-binding moiety, an FcRn-binding moiety, or an IgG-binding moiety. Embodiment 124. The complex of embodiment 123, wherein the half-life extension moiety is an albumin-binding moiety. Embodiment 125. The complex of embodiment 124, wherein the albumin-binding moiety is a peptide. Embodiment 126. The complex of embodiment 125, wherein the peptide has a linear amino acid sequence with at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 4, 266-267. Embodiment 127. The complex of embodiment 124, wherein the albumin-binding moiety comprises a fatty acid. Embodiment 128. The complex of embodiment 127, wherein the albumin-binding moiety comprises a bis-lipid. Embodiment 129. The complex of embodiment 128, wherein the bis-lipid is . FcRn- binding moiety. Embodiment 132. The complex of embodiment 131, wherein the FcRn-binding moiety is a peptide. Embodiment 133. The complex of embodiment 132, wherein the peptide has a linear amino acid sequence having at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 277 or 278. Embodiment 134. The complex of any of embodiments 88-133, wherein the oligomeric agent is single- stranded. Embodiment 135. The complex of embodiment 134, wherein the oligomeric agent is an RNAse H agent or a splice-modulating agent. Embodiment 136. The complex of any of embodiments 88-135, wherein the oligomeric agent comprises a second modified oligonucleotide consisting of 12-80 linked nucleosides, 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 137. The complex of embodiment 136, wherein the transferrin-receptor binding moiety is attached at the 3’-end of the second modified oligonucleotide, optionally through a first linker. Embodiment 138. The complex of embodiment 136, wherein the transferrin-receptor binding moiety is attached at the 5’-end of the second modified oligonucleotide, optionally through a first linker. Embodiment 139. The complex of any of embodiments 136-138, wherein the transferrin-receptor binding moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the second modified oligonucleotide, optionally through a first linker. Embodiment 140. The complex of any of embodiments 136-139, wherein half-life extension moiety is attached at the 3’-end of the second modified oligonucleotide, optionally through a second linker. Embodiment 141. The complex of any of embodiments 136-139, wherein half-life extension moiety is attached at the 5’-end of the second modified oligonucleotide, optionally through a second linker. Embodiment 142. The complex of any of embodiments 136-141, wherein the half-life extension moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the second modified oligonucleotide, optionally through a second linker. Embodiment 143. The complex of any of embodiments 136 or 140-142, wherein the transferrin- receptor binding moiety is attached at the 3’-end of the first modified oligonucleotide, optionally through a first linker. Embodiment 144. The complex of any of embodiments 136 or 140-142, wherein the transferrin- receptor binding moiety is attached at the 5’-end of the first modified oligonucleotide, optionally through a first linker. Embodiment 145. The complex of any of embodiments 136 or 140-144, wherein the transferrin- receptor binding moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a first linker. Embodiment 146. The complex of any of embodiments 136-139 or 143-145, wherein the half-life extension moiety is attached at the 3’-end of the first modified oligonucleotide, optionally through a second linker. Embodiment 147. The complex of any of embodiments 136-139 or 143-145, wherein the half-life extension moiety is attached at the 5’-end of the first modified oligonucleotide, optionally through a second linker. Embodiment 148. The complex of any of embodiments 136-139 or 143-147, wherein the half-life extension moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a second linker. Embodiment 149. The complex of any of embodiments 136-148, wherein the transferrin-receptor binding moiety and the half-life extension moiety are attached to the same modified oligonucleotide. Embodiment 150. The complex of any of embodiments 136-148, wherein the transferrin-receptor binding moiety is attached to the first modified oligonucleotide and the half-life extension moiety is attached to the second modified oligonucleotide. Embodiment 151. The complex of any of embodiments 136-148, wherein the transferrin-receptor binding moiety is attached to the second modified oligonucleotide and the half-life extension moiety is attached to the first modified oligonucleotide. Embodiment 152. The complex of embodiment any of embodiments 136-149, wherein the complex comprises a branching group, wherein the transferrin-receptor binding moiety is attached to the branching group, optionally through a first linker, and wherein the half-life extension moiety is attached to the branching group, optionally through a second linker. Embodiment 153. The complex of embodiment 152, wherein the branching group is attached at the 3’- end of the first modified oligonucleotide, optionally through a third linker. Embodiment 154. The complex of embodiment 152, wherein the branching group is attached at the 5’- end of the first modified oligonucleotide, optionally through a third linker. Embodiment 155. The complex of embodiment 152, wherein the branching group is attached at the 3’- end of the second modified oligonucleotide, optionally through a third linker. Embodiment 156. The complex of embodiment 152, wherein the branching group is attached at the 5’- end of the second modified oligonucleotide, optionally through a third linker. Embodiment 157. The complex of any of embodiments 136-156, wherein the pair of modified oligonucleotides is represented by one set of the following formulae: A‐L1‐X and T‐L2‐Y;  A‐L1‐X and Y‐L2‐T;  T‐L1‐X and A‐L2‐Y;  T‐L1‐X and Y‐L2‐T;  X‐L1‐A and T‐L2‐Y;  X‐L1‐T and A‐L2‐Y;  X‐L1‐T and Y‐L2‐A;  X‐L1‐A and Y‐L2‐T;  wherein A represents an albumin-binding moiety; T represents a transferrin-receptor binding moiety, X represents a first modified oligonucleotide (5’ to 3’), Y represents a second modified oligonucleotide (5’ to 3’); and each of L1and L2is an independently selected linker. Embodiment 158. The complex of any of embodiments 136-157, 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. Embodiment 159. The complex of any of embodiments 88-158, wherein the first modified oligonucleotide comprises at least one nucleoside comprising a modified sugar moiety. Embodiment 160. The complex of embodiment 152, wherein the first modified oligonucleotide comprises at least one nucleoside comprising a non-bicyclic modified sugar moiety. Embodiment 161. The complex of embodiment 160, wherein the non-bicyclic modified sugar moiety is a 2’-OMe sugar moiety, a 2’-MOE sugar moiety, a 2’-F sugar moiety, or a 2’-NMA sugar moiety. Embodiment 162. The complex of any of embodiments 159, wherein the first modified oligonucleotide comprises at least one nucleoside comprising a bicyclic sugar moiety. Embodiment 163. The complex of embodiment 162, wherein the bicyclic sugar moiety comprises a 4’- 2’ bridge selected from 4'-CH2-O-2' and 4'-CH(CH3)-O-2'. Embodiment 164. The complex of any of embodiments 136-163, wherein the second modified oligonucleotide comprises at least one nucleoside comprising a modified sugar moiety. Embodiment 165. The complex of embodiment 164, wherein the second modified oligonucleotide comprises at least one nucleoside comprising a non-bicyclic modified sugar moiety. Embodiment 166. The complex of embodiment 165, wherein the non-bicyclic modified sugar moiety a 2’-OMe sugar moiety, a 2’-MOE sugar moiety, a 2’-F sugar moiety, or a 2’-NMA sugar moiety. Embodiment 167. The complex of embodiment 164, wherein the second modified oligonucleotide comprises at least one nucleoside comprising a bicyclic sugar moiety. Embodiment 168. The complex of embodiment 167, wherein the bicyclic sugar moiety comprises a 4’- 2’ bridge selected from 4'-CH2-O-2' and 4'-CH(CH3)-O-2'. Embodiment 169. The complex of any of embodiments 88-168, wherein the first modified oligonucleotide comprises at least one modified internucleoside linkage. Embodiment 170. The complex of embodiment 169, wherein at least one internucleoside linkage of the first modified oligonucleotide is a phosphorothioate linkage. Embodiment 171. The complex of embodiment 169 or 170, wherein at least one internucleoside linkage of the first modified oligonucleotide is a phosphodiester linkage. Embodiment 172. The complex of any of embodiments 169-171, wherein at least one internucleoside linkage of the first modified oligonucleotide is a mesyl phosphoramidate internucleoside linkage. Embodiment 173. The complex of any of embodiments 88-172, wherein each internucleoside linkage of the first modified oligonucleotide is independently selected from a phosphodiester internucleoside linkage, a phosphorothioate internucleoside linkage, and a mesyl phosphoramidate internucleoside linkage. Embodiment 174. The complex of any of embodiments 136-173, wherein the second modified oligonucleotide comprises at least one modified internucleoside linkage. Embodiment 175. The complex of embodiment 174, wherein at least one internucleoside linkage of the second modified oligonucleotide is a phosphorothioate linkage. Embodiment 176. The complex of embodiment 174 or 175, wherein at least one internucleoside linkage of the second modified oligonucleotide is a phosphodiester linkage. Embodiment 177. The complex of any of embodiments 174-176, wherein at least one internucleoside linkage of the second modified oligonucleotide is a mesyl phosphoramidate internucleoside linkage. Embodiment 178. The complex of any of embodiments 174-177, wherein each internucleoside linkage of the second modified oligonucleotide is independently selected from a phosphodiester internucleoside linkage, a phosphorothioate internucleoside linkage, and a mesyl phosphoramidate internucleoside linkage. Embodiment 179. The complex of any of embodiments 88-178, wherein the oligomeric agent comprises nucleobases selected from uracil, thymine, cytosine, 5-methyl cytosine, adenine, guanine, and hypoxanthine. Embodiment 180. The complex of any of embodiments 88-179, wherein the first modified oligonucleotide consists of 12 to 20, 12 to 25, 13 to 20, 13 to 25, 14 to 20, 14 to 25, 15 to 20, 15 to 25, 16 to 18, 16 to 20, 16 to 25, 17 to 20, 17 to 25, 18 to 20, 18 to 25, 19 to 20, 19 to 25, 20 to 25, 20 to 3021-23, 21 to 25, 22 to 25, 23 to 25, 23 to 30, 18, 20, 21, or 23 linked nucleosides. Embodiment 181. The complex of any of embodiments 136-180, wherein the second modified oligonucleotide consists of 12 to 20, 12 to 25, 13 to 20, 13 to 25, 14 to 20, 14 to 25, 15 to 20, 15 to 25, 16 to 18, 16 to 20, 16 to 25, 17 to 20, 17 to 25, 18 to 20, 18 to 25, 19 to 20, 19 to 25, 20 to 25, 20 to 3021-23, 21 to 25, 22 to 25, 23 to 25, 23 to 30, 18, 20, 21, or 23 linked nucleosides. Embodiment 182. The complex of any of embodiments 136-181, wherein the oligomeric agent is an RNAi agent. Embodiment 183. The complex of embodiment 182, wherein the oligomeric agent comprises an antisense RNAi oligonucleotide and a sense RNAi oligonucleotide. Embodiment 184. The complex of any of embodiments 1-183, wherein the complex has a total molecular weight of less than 50 kD, less than 40 kD, less than 30 kD, less than 20 kD, or less than 10 kD. Embodiment 185. The complex of any of embodiments 1-184, wherein the complex has a total molecular weight of 1 kD to 50 kD, 5 kD to 50 kD, 5 kD to 40 kD, 5 kD to 30 kD, 5 kD to 20 kD, 10 kD to 50 kD, 10 kD to 40 kD, 10 kD to 30 kD, 10 kD to 20 kD, or 15 kD to 25 kD. Embodiment 186. A method of modulating the expression of a target nucleic acid in the CNS, comprising administering a complex of any of embodiments 88-185 to a subject. Embodiment 187. A method of modulating the expression of a target nucleic acid in muscle, comprising administering a complex of any of embodiments 88-185 to a subject. Embodiment 188. A method of modulating the expression of a target nucleic acid in peripheral nerve tissue, comprising administering a complex of any of embodiments 88-185 to a subject. Embodiment 189. The method of any of embodiments 186-188, wherein the complex is administered systemically. Embodiment 190. The method of embodiment 189, wherein the complex is administered intravenously. Embodiment 191. The method of embodiment 189, wherein the complex is administered subcutaneously. Embodiment 192. The complex of any of embodiments 1-185, for use in therapy. Embodiment 193. The complex of any of embodiments 1-185, for use in the manufacture of a medicament. Complexes for Blood Brain Barrier Delivery of Cargo Provided herein are complexes comprising at least one half-life extension moiety, at least one transferrin receptor binding moiety, and at least one cargo. In certain embodiments, the half-life extension moiety is selected from an albumin binding moiety, an FcRn binding moiety, and an IgG binding moiety. In certain embodiments, the albumin binding moiety is selected from a peptide, a cyclic peptide, a bicyclic peptide, a fatty acid, or a lipid. In certain embodiments, the half-life extension moiety does not comprise the Fc domain of an antibody. In certain embodiments, the transferrin receptor binding moiety is selected from a peptide, a cyclic peptide, a bicyclic peptide, a VNAR, a VHH, an aptamer, or a small molecule. In certain embodiments, the transferrin receptor binding moiety does not comprise ScFv or the Fc domain of an antibody. In certain embodiments, the cargo is an oligomeric agent. In certain embodiments, the oligomeric agent is a single-stranded modified oligonucleotide. In certain embodiments, the oligomeric agent is a duplex comprising two complementary modified oligonucleotides. In certain embodiments, a modified oligonucleotide is covalently attached to a half-life extension moiety through a linker covalently attached to the 5’-end of the oligonucleotide. In certain embodiments, an oligomeric compound is covalently attached to a half-life extension moiety through a linker covalently attached to the 3’-end of the oligonucleotide. In certain embodiments, an oligomeric compound is not covalently attached to a half-life extension moiety. In certain embodiments, an oligomeric compound is covalently attached to a transferrin receptor binding moiety through a linker covalently attached to the 3’-end of the oligonucleotide. In certain embodiments, an oligomeric compound is covalently attached to a transferrin receptor binding moiety through a linker covalently attached to the 5’-end of the oligonucleotide. In certain embodiments, an oligomeric compound is covalently attached to a half-life extension moiety and / or a transferrin receptor binding moiety at an internal position, for instance, the 2’-position of a ribosyl 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 oligomeric compound comprising 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 Protein Binding Moieties In certain embodiments, complexes provided herein comprise a protein binding moiety. In certain embodiments, the half-life extension moiety is a protein binding moiety. In certain embodiments, complexes comprise a transferrin receptor binding moiety. In certain embodiments, complexes comprise an albumin binding moiety, an FcRn binding moiety, or an IgG binding moiety. In certain embodiments, a protein binding moiety is a polypeptide, a peptide, an aptamer, or another non-peptide ligand. In certain embodiments, the peptide is a linear peptide, a cyclic peptide, or a bicyclic peptide. In certain embodiments, the polypeptide is the antigen binding fragment of a shark antibody (VNAR) or the antigen binding fragment of a camelid antibody (VHH). Linear or Cyclic Peptides In certain embodiments, a protein binding moiety is a linear, cyclic, or bicyclic peptide. Linear, cyclic, and bicyclic peptides can be designed and selected using multiple rounds of in vitro mRNA display and in vitro selection. Techniques for the discovery of high-affinity cyclic peptides utilizing in vitro translation and display have been previously described in detail – see, e.g., Tsiamantas, et al, Methods in Mol. Biol., vol.2001, 2019; Li, et al., Molecular Biotech, 61:60-71, 2019; Blanco et al., Phys. Chem. Chem. Phys., 22(12):6492-6506; Linciano, et al., MedChemComm.¸10(9)1569-1580, 2019; Lee, et al., Nature Comm., 10:5097, 2019; Passioura, et al., Kashiwagi, et al., WO2011 / 049157; Suga, et al., WO2008 / 117833; Nemoto, et al., WO2006 / 141194; Szostak, et al., WO2000 / 047775; Suga, et al., WO2007 / 066627. Further techniques for the display and selection of bicyclic peptides have been previously described – see, e.g., Heinis et al. (2009), Nat. Chem. Biol.5(7), 502-7, 2009; WO 2009 / 098450; Heinis et al., Angewandte Chemie, International Edition 53(6) 1602-1606, 2014). Aptamers In certain embodiments, a protein binding moiety is an aptamer. Aptamers are short oligonucleotides that bind with high affinity and specificity to proteins, peptides, or small molecules. Aptamers typically have defined secondary and tertiary structure owing to their propensity to form complementary base pairs, and often fold into intricate three-dimensional molecular structures. Aptamers can be selected in vitro from very large libraries of randomized sequences by the process of systemic evolution of ligands by exponential enrichment (SELEX; described in Ellington and Szostak, Nature, 346: 818-822, 1990; Tuerk and Gold, Science, 249 : 505-510, 1990) or by developing SOMAmers (slow off – rate modified aptamers ) (Gold L et al . PLoS ONE 5(12): e15004, 2010). Applying the SELEX and the SOMAmer technology includes for instance adding functional groups that mimic amino acid side chains to expand the aptamer’s chemical diversity. As a result, high affinity aptamers for almost any protein target are enriched and identified. Aptamers that recognize the transferrin receptor have been previously described; see, e.g., US 9,439,973; WO2020 / 245198; US 11,427,826; Zhang, et al., Int. J. Mol. Sci., 2021). Small Protein Ligands Centyrins In certain embodiments, a protein binding moiety is a centyrin, a polypeptide based on the fibronectin type III domains. The FN3 domains that specifically bind to a cell-surface receptor may be isolated by producing a FN3 library (e.g., those described in WO2021 / 076546) using cis display to ligate DNA fragments encoding the scaffold proteins to a DNA fragment encoding RepA to generate a pool of protein- DNA complexes formed after in vitro translation wherein each protein is stably associated with the DNA that encodes it (U.S. Pat. No.7,842,476; Odegrip et.al., Proc Natl Acad Sci,101, 2806-2810, 2004), and assaying the library for specific binding to the cell-surface receptor. Exemplary well-known methods which can be used are ELISA, sandwich immunoassays, and competitive and non-competitive assays (see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol.1, John Wiley & Sons, Inc., New York). The identified FN3 domains that specifically bind to a cell-surface target are further characterized for their binding to the cell-surface target, modulation of target activity, internalization, stability, and other desired characteristics. The FN3 domains that specifically bind a cell-surface target may be generated using any FN3 domain as a template to generate a library and screening the library for molecules specifically binding a cell surface-target. Nanofitins In certain embodiments, a protein binding moiety is a nanofitin, a variant of a Sac7d family. Nanofitins having various binding partners and affinities may be selected via previously described methods (see e.g. WO2021 / 180823). In certain embodiments, a nanofitin has affinity for the transferrin receptor. De Novo Protein Scaffolds In certain embodiments, a protein binding moiety can be engineered de novo, as described by Sahtoe, et al., Biophys. and Comp. Biol, 2021. This method uses computational modeling to design beta sheet polypeptides for interactions with similar beta sheet protein domains contained within native proteins. Such de novo protein designs have been used to target the transferrin receptor (WO 2022 / 026555). Cysteine-Dense Peptides In certain embodiments, a protein binding moiety is a “cysteine-dense peptide” (CDP), a polypeptide having ~50 amino acids. CDPs that target a specific receptor can be identified via a mammalian display system that has been previously described (Crook, et al., Nature Comm., 2017), in a similar fashion to selecting for FN3 domains described above. CDPs that target the transferrin receptor have been previously described (see, e.g., WO2020 / 123032). Various other protein scaffolds for targeted evolution of small protein ligands have been previously described, including, but not limited to, affibodies, adhirons, adnectins (also known as monobodies), affilin, affimers, alphabodies, anticalin, armadillo repeat proteins, atrimer (also known as tetranectin), avimer (also known as maxibody), DARPin, fyomers, Kunitz domain proteins, Obodies, pronectin, and repebodies. Such scaffolds can be engineered to bind at a site on the transferrin type 1 receptor via known methods (see, e.g., Skrlec, et al., Trends in Biotech, 2015; Shipunova and Deyev, Acta Naturae, 2022; Tomoyuki, et al., Chem. Lett., 2021; Bonadio and Shifman, Prot. Engineering, Design and Selection, 2021). Antibody Fragments In certain embodiments, a protein binding moiety is an antigen binding fragment of a shark antibody (VNAR) or an antigen binding fragment of a camelid antibody (VHH). Methods for generating VNAR and VHH that specifically bind to a specific protein are previously described; see, e.g., US 11,512,136; Manoutcharian, Fish Shellfish Immunol, 2023; Lim, et al, Fish Shellfish Immunol, 2023; Tang, et al., Int. J. Mol. Sci., 2023; Yong Joon Kim, et al., Adv. Drug Deliv. Rev., 2023; Kovaleva, et al, Expert Opin. Biol. Ther., 2014; Zheng, et al., Front. Immunol., 2023; Liu and Yang, Int. J. Mol. Sci, 2023; Nuttall, Methods Mol. Biol, 2012). In certain embodiments, a protein binding moiety is a peptide or protein. In certain embodiments, the protein binding moiety comprises no more than 10, no more than 11, no more than 12, no more than 13, no more than 14, no more than 15, no more than 16, no more than 17, no more than 18, no more than 19, no more than 20, no more than 21, no more than 22, no more than 23, no more than 24, or no more than 25 amino acids or amino acid mimetics. In certain embodiments, the protein binding moiety comprises no more than 25, no more than 30, no more than 35, no more than 40, no more than 45, no more than 50, no more than 55, no more than 60, no more than 65, no more than 70, no more than 75, no more than 80, no more than 85, no more than 90, no more than 95, no more than 100, no more than 105, no more than 110, no more than 115, no more than 120, no more than 125, no more than 130, no more than 135, no more than 140, no more than 145, or no more than 150 amino acids or amino acid mimetics. In certain embodiments, the protein binding moiety comprises 12-22 amino acids. In certain embodiments, the protein binding moiety is a bicyclic peptide with a linear amino acid sequence comprising 12-22 linked amino acids. In certain embodiments, the protein binding moiety comprises 105-140 amino acids. In certain embodiments, the protein binding moiety is a VHH comprising 105-140 amino acids. In certain embodiments, the protein binding moiety has a molecular weight that is less than 15 kD, less than 14 kD, less than 13 kD, less than 12 kD, less than 11 kD, less than 10 kD, less than 9 kD, less than 8 kD, less than 7 kD, less than 6 kD, less than 5 kD, less than 4 kD, less than 3 kD, less than 2 kD, less than 1.5 kD, or less than 1 kD. In certain embodiments, the protein binding is a protein with a molecular weight of 12 kD-15 kD. In certain embodiments, the protein binding moiety is a peptide with a molecular weight of less than 2 kD. In certain embodiments, the protein binding moiety is a peptide with a molecular weight between 1 kD and 2 kD.     Certain Transferrin Receptor Binding Moieties In certain embodiments, the protein binding moiety is a centyrin, nanofitin, de novo protein, cysteine- dense peptide, or other small protein ligand that recognizes a cell surface protein. In certain instances, the cell- targeting moiety is a centyrin, nanofitin, de novo protein, cysteine-dense peptide, or other small protein ligand that recognizes a cell surface protein on a cell of the blood-brain barrier. In certain embodiments, the cell surface protein is the 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 complexes for both muscle and CNS delivery of various cargoes. Representative cargoes include antibodies and antibody fragments, cytotoxic 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). In certain embodiments, the transferrin receptor binding moiety is the antigen binding fragment of a shark antibody (VNAR) or the antigen binding fragment of a camelid antibody (VHH). In certain embodiments, the transferrin receptor binding moiety is or the antigen binding fragment of a camelid antibody (VHH). In certain embodiments, the transferrin receptor binding moiety is a peptide or a protein. In certain embodiments, the transferrin receptor binding moiety comprises no more than 10, no more than 11, no more than 12, no more than 13, no more than 14, no more than 15, no more than 16, no more than 17, no more than 18, no more than 19, no more than 20, no more than 21, no more than 22, no more than 23, no more than 24, or no more than 25 amino acids or amino acid mimetics. In certain embodiments, the transferrin receptor binding moiety comprises no more than 25, no more than 30, no more than 35, no more than 40, no more than 45, no more than 50, no more than 55, no more than 60, no more than 65, no more than 70, no more than 75, no more than 80, no more than 85, no more than 90, no more than 95, no more than 100, no more than 105, no more than 110, no more than 115, no more than 120, no more than 125, no more than 130, no more than 135, no more than 140, no more than 145, or no more than 150 amino acids or amino acid mimetics. In certain embodiments, the transferrin receptor binding moiety comprises 12-22 amino acids. In certain embodiments, the transferrin receptor binding moiety is a bicyclic peptide with a linear amino acid sequence comprising 12-22 linked amino acids. In certain embodiments, the transferrin receptor binding moiety comprises 105-140 amino acids. In certain embodiments, the transferrin receptor binding moiety is a VHH comprising 105-140 amino acids. In certain embodiments, the transferrin receptor binding moiety has a molecular weight that is less than 15 kD, less than 14 kD, less than 13 kD, less than 12 kD, less than 11 kD, less than 10 kD, less than 9 kD, less than 8 kD, less than 7 kD, less than 6 kD, less than 5 kD, less than 4 kD, less than 3 kD, less than 2 kD, less than 1.5 kD, or less than 1 kD. In certain embodiments, the transferrin receptor binding moiety is a protein with a molecular weight of 12 kD-15 kD. In certain embodiments, the transferrin receptor binding moiety is a peptide with a molecular weight of less than 2 kD. In certain embodiments, the transferrin receptor binding moiety is a peptide with a molecular weight between 1 kD and 2 kD. Selected transferrin receptor binding moieties are listed in the table below. Table 1 Selected transferrin receptor binding moieties TfR TfR binding binding et name moietTfR binding m SEQmoioietyID NOReference. : l ): 1 t, ic 0 S, , , 2 nn ARVDQTPQTITKETGESLTINCVLRDSNCALSS TYWYRKKSGSTNEENISKGGRYVETVNSGSK Clone C VNARWO2016 / 0778SFSLRINDLTVEDSGTYRCNVVQYPSYNNYFW263 4085 shark antibody (VNAR) or the antigen binding fragment of a camelid antibody (VHH). In certain embodiments, the transferrin receptor binding moiety is the antigen binding fragment of a camelid antibody (VHH). In certain embodiments, the transferrin receptor binding moiety is a VHH selected from any of SEQ ID NOs: 4522-4550. In certain embodiments, the transferrin receptor binding moiety is a centyrin polypeptide, selected from any of SEQ ID Nos: 300-844. In certain embodiments, the transferrin receptor binding moiety is a de novo protein, selected from any of SEQ ID Nos: 845-866. In certain embodiments, the transferrin receptor binding moiety is a bicyclic peptide. In certain embodiments, the bicyclic peptide is a bicycle ligand. In certain embodiments, a bicyclic peptide comprises a peptide comprising at least three reactive groups, separated by at least two loop sequences, and a molecular scaffold which forms covalent bonds with the reactive groups of the polypeptide such that at least two polypeptide loops are formed on the molecular scaffold, and is a bicycle ligand. In certain embodiments, the molecular scaffold is 1,1',1''-(1,3,5-triazinane-1,3,5-triyl)triprop-2-en-1-one (TATA). In certain embodiments, the molecular scaffold is 1,1',1''-(1,3,5-triazinane-1,3,5-triyl)tris(2-bromoethanone) (TATB). In certain embodiments, reactive groups are cysteines. In certain embodiments, loop sequences comprise 2, 3, 4, 5, 6, 7, 8, or 9 amino acids. In certain embodiments, loop sequences comprise three cysteine residues separated by two loop sequences, the first of which consists of 2 amino acids and the second of which consists of 9 amino acids. In certain embodiments, the loop sequences comprise three cysteine residues by two loop sequences both of which consist of 6 amino acids. In certain embodiments, the loop sequences comprise three cysteine residues separated by two loop sequences the first of which consists of 3 amino acids and the second of which consists of 8 amino acids. In certain embodiments, the loop sequences comprise three cysteine residues separated by two loop sequences the first of which consists of 7 amino acids and the second of which consists of 3 amino acids. In certain embodiments, a bicyclic peptide comprises an amino acid sequence selected from: CiXXCiiXXXXXXXXXCiii; CiXXXXXXCiiXXXXXXCiii; CiXXXCiiXXXXXXXXiii; or CiXXXXXXXCiiXXXCiii;wherein Ci, Ciiand Ciiirepresent first, second and third cysteine residues, respectively, and each “X” represents an independently selected natural or non-natural amino acid, or a pharmaceutically acceptable salt thereof. In certain embodiments, a bicycle ligand further comprises an N-terminal extension and / or a C- terminal extension. In certain embodiments, a bicyclic peptide comprises an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to any of the following sequences: CiSPDAHLGCiiISYCiii(SEQ ID NO: 21); CiSPDAYLGCiiISYCiii(SEQ ID NO: 22); CiP[HyP]DAYLGCiiISYCiii(SEQ ID NO: 23); CiS[HyP]DAHLGCiiISYCiii(SEQ ID NO: 24); CiS[Aze]DAHLGCiiISYCiii(SEQ ID NO: 25); CiP[HyP]DAYLGCii[tBuGly]SYCiii(SEQ ID NO: 26); Ci[K(N3)]PDAHLGCiiISYCiii(SEQ ID NO: 27); CiS[K(N3)]DAHLGCiiISYCiii(SEQ ID NO: 28); or CiSPD[K(N3)]HLGCiiISYCiii(SEQ ID NO: 29); Ci, Ciiand Ciiirepresent first, second and third cysteines, respectively; [HyP] represents 4-trans-hydroxy-L- proline; [Aze] represents azetidine-2-carboxylic acid; [tBuGly] represents t-butyl glycine; and [K(N3)] represents 6-azido lysine. In certain embodiments, a bicycle ligand further comprises an N-terminal extension and / or a C-terminal extension. In certain embodiments, a bicycle ligand comprises an amino acid sequence of: CiXXDXXXGCiiISYCiii(SEQ ID NO: 30); wherein each X is independently selected from natural or non- natural amino acid, or a pharmaceutically acceptable salt thereof. In certain embodiments, a bicycle ligand further comprises an N-terminal extension and / or a C-terminal extension. In certain embodiments, a bicycle ligand comprises the following structure, wherein each Xaa is an independently selected amino acid side chain; each Baa is an independently selected amino acid or amino acid mimetic; n is from 0 to 5; m is from 3 to 7; o is from 3 to 7; p is from 0 to 5; wherein the sum of m+o is less than 12. In certain embodiments, a linker is attached through the N-terminus, the C-terminus, or through one of the loop amino acids. In certain embodiments, a linker is attached through the side chain of an N-terminal or C-terminal amino acid. In certain embodiments, a bicycle ligand comprises the formula [Zi]-[J]m-[Zii]-[O]o-[Ziii]. In certain embodiments, a bicycle ligand comprises the following structure: is an independently selected amino acid or amino acid mimetic; m is from 3 to 7 and; o is from 3 to 7. In certain embodiments, a bicycle ligand further comprises an N-terminal extension and / or a C- terminal extension. In certain embodiments, a linker is attached through the N-terminus, the C-terminus, or through one of the loop amino acids. In certain embodiments, a linker is attached through a side chain of a loop amino acid. In certain embodiments, a linker is attached through the side chain of an N-terminal or C-terminal amino acid. In certain embodiments, a bicycle ligand comprises or consists of a sequence selected from the following table: Table 2 Selected Bicycle Transferrin Receptor Binding Moieties N- Bi l N b t i lSEQ ID BCY15889 Ac CPPDAHLGCISWC 36 BCY15467 none ACPQDAYLGCISWCA 37 BCY17874 AzPro CSPDAHLGCISYCEPW 48 BCY17868 Ac CSPDAHLGCISYC[K(N3)] 65 BCY16046 none ACSPDAHLGC[EPA]SYCA 95 BCY16964 none ACPPDAYLGC[tBuGly]SYCA 96 BCY16040 none ACSPDAHLGC[B-MeIle]SYCA 131 BCY15771 none ACSADAHLGCISYCA[Sar]6[K-Fl] 132 BCY23204 none CP[HyP]DAYLGC[tBuGly]SYCE[HyP]W 166 BCY23205 none CP[HyP]DAYLGC[tBuGly]SYCE[Oxa]W 167 w represents aminoisobutyric acid, Aze represents azetidine-2-carboxylic acid, B-MeIle represents beta-methyl isoleucine, C5g represents cyclopentyl glycine, Cba represents β-cyclobutylalanine, Cbg represents cyclobutyl glycine, Chg represents cyclohexyl glycine, Cpg represents cyclopropyl glycine, EPA represents 2-amino-3-ethyl-pentanoic acid, HyP represents trans-4-hydroxy-L-proline, K(N3) represents 6-azido lysine, 1Nal represents 1-naphthylalanine, 2Nal represents 2-naphthylalanine, 4Pal represents 4-pyridylalanine, Pip represents pipecolic acid; tBuAla represents t-butyl-alanine, tBuGly represents t-butyl-glycine, 3tBuTyr represents 3-t-Butyl-Tyrosine, Sar represents sarcosine, K-Fl represents fluorescein attached at the 6-position of a lysine, Fl-G represents fluorescein attached at the N-terminus of a glycine, NMeTrp represents N-methyl tryptophan, dP representsD-proline, dA representsD-alanine, dW representsD-tryptophan, dS representsD- serine, dT representsD-threonine, dD representsD-aspartic acid, dN representsD-asparagine, dQ representsD- glutamine, Cis-HyP represents cis-L-4-hydroxyproline, DOPA represents 3,4-dihydroxy-phenylalanine, Gla represents L-γ-carboxyglutamic acid, HSer represents homoserine, hTyr represents homo-tyrosine, 3HyV represents 3-hydroxy-L-valine, Oxa represents oxazolidine-4-carboxylic acid, pCaPhe represents L-4- carbamoylphenylalanine, pCoPhe represents 4-carboxy-L-phenylalanine, K(PYA) represents N-pentynoyl-L- lysine, [PEGXX] represents poly(ethylene glycol), where XX is the number of ethylene glycol units, and [K(N3)(PYA-Maleimide)] represents a modified lysine having the following structure: HON O O O . In certain embodiments, a bicycle ligand has the structure: linker (SEQ ID NO: 193). In certain embodiments, the molecular scaffold is 1,1',1''-(1,3,5-triazinane-1,3,5-triyl)tris(2-bromoethanone) (TATB). In certain embodiments, X is a linker that attaches the bicycle ligand to the remainder of a complex, optionally via a branching group. In certain embodiments, the bicycle ligand comprises a C-terminal CONH2group (a C-terminal amide). In certain embodiments, the bicycle ligand comprises an N-terminal acetyl group and a C-terminal CONH2group. In certain embodiments, a bicycle ligand comprises an amino acid sequence which is selected from CP[HyP]DAYLGC[tBuGly]SYCEPW (SEQ ID NO: 3, herein referred to as BCY17995) and CP[HyP]DAHLGC[tBuGly]SYC (SEQ ID NO: 2, herein referred to as B191), wherein HyP represents trans- 4-hydroxy-L-proline and tBuGly represents t-butyl-glycine. In certain embodiments, the bicycle ligand comprises an N-terminal acetyl group and a C-terminal CONH2group. In certain embodiments, the first, second, and third cysteine residues within the bicycle ligand are covalently bonded to a molecular scaffold such that two polypeptide loops are formed on the molecular scaffold. In certain embodiments, the molecular scaffold is 1,1',1''-(1,3,5-triazinane-1,3,5-triyl)triprop-2-en-1-one (TATA). In certain embodiments, the molecular scaffold is 1,1',1''-(1,3,5-triazinane-1,3,5-triyl)tris(2-bromoethanone) (TATB). In certain embodiments, the transferrin receptor binding moiety is a bicycle ligand, selected from any of SEQ ID Nos: 21-29 or 31-191, wherein the molecular scaffold is TATB. In certain embodiments, the transferrin receptor binding moiety comprises a bicycle ligand, selected from any of SEQ ID Nos: 21-29 or 31-191, wherein the molecular scaffold is TATB, and an N-terminal and / or a C-terminal extension. In certain embodiments the N-terminal extension is selected from A–; [Fl-G][Sar5]–A–; N[1Nal]N–; NWN–; N[dW]N–; HWM–; NEV–; HTS–; N[NMeTrp]N–; ESF–; [AzPro]–NWN–; [AzPro]–; and N[dY]N– , wherein an N-terminal amino acid comprises an optional N-acetyl; wherein [dW] is d-tryptophan, [Sar] is sarcosine, [AzPro] is azidopropyl, [NMeTrp] is N-methyl-tryptophan, [1Nal] is 1-naphthylalanine, [dY] is d- tyrosine, and [Fl-G] represents fluorescein attached at the N-terminus of a glycine. In certain embodiments the C-terminal extension is selected from –A; –E[Pip]W; –EPW; –E[Aze]W; –E[dP]W; –PHP; –PIVH; –EHQE; –[K(N3)]; –EPW–[K(N3)]; –E–[dP]–W–[K(N3)]; –E–[Aze]–W– [K(N3)]; –E–[Pip]–W–[K(N3)]; –[K(N3)(PYA–maleimide]; –EPW–[PEG10]–[K(N3)]; –EPW–[PEG24]– [K(N3)]; and –EPWGGSGGS–[K(N3)], wherein [Pip] is pipecolic acid, [Aze] is azetidine-2-carboxylic acid, [dP] is D-proline, K(N3) is 6-azido lysine, and [K(N3)(PYA-Maleimide)] is as defined herein. In certain embodiments, the transferrin receptor binding moiety is capable of interacting with the type 1 transferrin receptor. Generally, the interaction is reversible and no covalent bonds are formed. In certain embodiments, the transferrin receptor binding moiety 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 binding moiety 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 moiety has affinity for the binding site of transferrin. In certain embodiments, the transferrin receptor binding moiety has affinity for Tfr1 at a site different from the binding site of transferrin. In certain embodiments, the transferrin receptor binding moiety does not cause dimerization of the type 1 transferrin receptor. In certain embodiments, a transferrin receptor binding moiety is capable of being internalized when it interacts with or binds the transferrin receptor. In certain embodiments, a transferrin receptor binding moiety is capable of delivering a cargo to a cell when it interacts with or binds the transferrin receptor. Certain Half-Life Extension Moieties In certain embodiments, complexes provided herein comprise a half-life extension moiety. In certain embodiments, a half-life extension moiety is selected from an albumin binding moiety, an FcRn binding moiety, and an IgG binding moiety. In certain embodiments, the half-life extension moiety does not comprise the Fc domain of an antibody. In certain embodiments, the half-life extension moiety has a molecular weight that is less than 15 kD, less than 14 kD, less than 13 kD, less than 12 kD, less than 11 kD, less than 10 kD, less than 9 kD, less than 8 kD, less than 7 kD, less than 6 kD, less than 5 kD, less than 4 kD, less than 3 kD, less than 2 kD, less than 1.5 kD, less 1000 kDa, less than 900 kDa, less than 800 kDa, less than 700 kDa, less than 600 kDa, less than 500 kDa, less than 400 kDa, or less than 300 kDa. Albumin Binding Moieties In certain embodiments, a half-life extension moiety is an albumin binding moiety. In certain embodiments, the albumin binding moiety is selected from a peptide, a cyclic peptide, a bicyclic peptide, a fatty acid, or a lipid. In certain embodiments, the albumin binding moiety is a peptide or a protein. In certain embodiments, the albumin binding moiety comprises no more than 10, no more than 11, no more than 12, no more than 13, no more than 14, no more than 15, no more than 16, no more than 17, no more than 18, no more than 19, no more than 20, no more than 21, no more than 22, no more than 23, no more than 24, or no more than 25 amino acids or amino acid mimetics. In certain embodiments, the albumin binding moiety comprises no more than 25, no more than 30, no more than 35, no more than 40, no more than 45, no more than 50, no more than 55, no more than 60, no more than 65, no more than 70, no more than 75, no more than 80, no more than 85, no more than 90, no more than 95, no more than 100, no more than 105, no more than 110, no more than 115, no more than 120, no more than 125, no more than 130, no more than 135, no more than 140, no more than 145, or no more than 150 amino acids or amino acid mimetics. In certain embodiments, the albumin binding moiety comprises 12-22 amino acids. In certain embodiments, the albumin binding moiety is a bicyclic peptide with a linear amino acid sequence comprising 12-22 linked amino acids. In certain embodiments, the albumin binding moiety comprises 105-140 amino acids. In certain embodiments, the albumin binding moiety is a VHH comprising 105-140 amino acids. In certain embodiments, the albumin binding moiety is a peptide or protein with a molecular weight that is less than 15 kD, less than 14 kD, less than 13 kD, less than 12 kD, less than 11 kD, less than 10 kD, less than 9 kD, less than 8 kD, less than 7 kD, less than 6 kD, less than 5 kD, less than 4 kD, less than 3 kD, less than 2 kD, less than 1.5 kD, or less than 1 kD. In certain embodiments, the albumin binding moiety is a protein with a molecular weight of 12 kD-15 kD. In certain embodiments, the albumin binding moiety is a peptide with a molecular weight of less than 2 kD. In certain embodiments, the albumin binding moiety is a peptide with a molecular weight between 1 kD and 2 kD. In certain embodiments, the albumin binding moiety is a fatty acid or comprises a fatty acid. In certain such embodiments, the albumin binding moiety has a molecular weight of less than 1000 kDa, less than 900 kDa, less than 800 kDa, less than 700 kDa, less than 600 kDa, less than 500 kDa, less than 400 kDa, or less than 300 kDa. Certain albumin binding moieties are provided in the table below. Table 3 Certain Albumin Binding Moieties Albumin Albumin binding binding Alb i bi di i tSEQ IDRf9 867-996 (see US 11,203,630) or 997-999 (see WO 2017 / 210425). In certain embodiments, the albumin binding moiety is a peptide, selected from any of SIDs: 1000-1257 (see WO 2009 / 016043), any of SIDs 1258-1460 (see WO 2012 / 004384), any of SIDs 4400-4429 (see WO 2013 / 177398), any of SIDs 1461-1488 (see WO 2014 / 048977), or any of SIDs 1489-3269 (see WO2015 / 091957). In certain embodiments, the albumin binding moiety is an ankyrin repeat domain, selected from any of SIDs 3270-3286 (see WO 2016 / 156596). In certain embodiments, the albumin binding moiety is a VHH domain, selected from any of SIDs 3287-3293 (see WO 2017 / 201488) or any of SIDs 3294-3356 (see WO2018 / 104444). In certain embodiments, the albumin binding domain is an ScFv, selected from any of SIDs 4430-4437 (see WO2012 / 162068). In certain embodiments, the albumin binding domain is a nanofitin, selected from any of SIDs 292-299 (see WO2022 / 171852). Additional albumin-binding moieties are described in Bioorg Med Chem Lett, 2002, 12(20), 2883-6, Bioorg Med Chem Lett, 2003, 13(9), 1513-5, Int J Pep Res Ther, 2007, 13(1-2), 12, Theranostics, 2016, 6(2), 243-53, J Med Chem 2017, 60(17), 7434-46, J Med Chem 2017, 60(17), 7434-46, Pharm Res 2006, 23(1), 49-55, Angew Chem Int Ed, 2008, 47(17), 3196-3201, Eur J Nucl Med Mol Imaging 2018, 45(11), 1841-51), J Nucl Med 2019, 60(5), 656-63, Mol Pharmaceutics 2018, 15, 2297-306, Mol Pharmaceutics 2018, 15, 5556-64, EP 3778592, Diabetes Care 2002; 25:1398-1404, Med Chem; 2015, 58, 7370-7380, WO 2020 / 205948, WO 2008 / 053360, and Bioconjugate Chem 2017, 28(9), 2372-2383, each of which is incorporated by reference. In certain embodiments, an albumin binding moiety comprises a fatty acid. In certain embodiments, an albumin binding moiety comprises a saturated or unsaturated C10, C12, C14, C16, C18, C20, C22, C24, C26, C28, or C30 fatty acid. In certain embodiments, an albumin binding moiety comprises a saturated or unsaturated C16 or C18 fatty acid. In certain embodiments, the fatty acid is straight chain or branched. In certain embodiments, an albumin binding moiety comprises: . In certain embodiments, an albumin binding moiety comprises myristic acid, hexadecenoic acid, octadecanoic acid, octadecanoic diacid, palmitic acid, palmitic diacid, 16-tetrazole-hexadecanoic acid, 16- sulfo-hexadecanoic acid, docosanoic diacid, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, lauric acid, dimeric lauric acid, tetrameric lauric acid, α, ω-octadecanoic diacid (see Linciano, et al, J. Controlled Release, 2022). Also provided in various embodiments are lipid conjugates and substituents as described in one or more of WO2016161374, WO2019217459, WO2020257194, WO2021092371, WO2023064530, WO2024129748, or WO2024148329, each of which is incorporated by reference. In certain embodiments, the albumin binding moiety comprises two or more fatty acids. In certain embodiments, the albumin binding moiety comprises a bis-lipid in which two fatty acids are attached by branching group, and each fatty acid is optionally attached through a linker. In certain embodiments, each fatty acid of the bis-lipid is a C16. In certain embodiments, the bis-lipid is . a C18 diacid: .  FcRn Binding Moieties In certain embodiments, a half-life extension moiety is an FcRn binding moiety. In certain embodiments, the FcRn binding moiety is a peptide or a protein. In certain embodiments, the FcRn binding moiety comprises no more than 10, no more than 11, no more than 12, no more than 13, no more than 14, no more than 15, no more than 16, no more than 17, no more than 18, no more than 19, no more than 20, no more than 21, no more than 22, no more than 23, no more than 24, or no more than 25 amino acids or amino acid mimetics. In certain embodiments, the FcRn binding moiety comprises no more than 25, no more than 30, no more than 35, no more than 40, no more than 45, no more than 50, no more than 55, no more than 60, no more than 65, no more than 70, no more than 75, no more than 80, no more than 85, no more than 90, no more than 95, no more than 100, no more than 105, no more than 110, no more than 115, no more than 120, no more than 125, no more than 130, no more than 135, no more than 140, no more than 145, or no more than 150 amino acids or amino acid mimetics. In certain embodiments, the FcRn binding moiety comprises 12-22 amino acids. In certain embodiments, the FcRn binding moiety is a bicyclic peptide with a linear amino acid sequence comprising 12-22 linked amino acids. In certain embodiments, the FcRn binding moiety comprises 105-140 amino acids. In certain embodiments, the FcRn binding moiety is a VHH comprising 105-140 amino acids. In certain embodiments, the FcRn binding moiety is a peptide or protein with a molecular weight that is less than 15 kD, less than 14 kD, less than 13 kD, less than 12 kD, less than 11 kD, less than 10 kD, less than 9 kD, less than 8 kD, less than 7 kD, less than 6 kD, less than 5 kD, less than 4 kD, less than 3 kD, less than 2 kD, less than 1.5 kD, or less than 1 kD. In certain embodiments, the FcRn binding moiety is a protein with a molecular weight of 12 kD-15 kD. In certain embodiments, the FcRn binding moiety is a peptide with a molecular weight of less than 2 kD. In certain embodiments, the FcRn binding moiety is a peptide with a molecular weight between 1 kD and 2 kD. Certain FcRn binding moieties are provided in the table below. Table 4 Certain FcRn binding moieties FcRn FcRn binding binding FcRn bindin moiet SEQReference0 0 6 l., 2 Indicates that two amino acids are joined by a disulfide bond. In certain embodiments, the FcRn binding moiety is a cyclic peptide selected from any of SEQ ID NOs 3357-3671 (see WO2007 / 098420) or SEQ ID NOs 4438-4521 (see WO2014 / 205072). In certain embodiments, the FcRn binding moiety comprises or consists of a peptide selected from any of SEQ ID NOs: 3672-4024 (see WO2014 / 140366). In certain embodiments, the FcRn binding moiety is a peptide comprising two FcRn binding regions, wherein each FcRn binding region is selected from any of SEQ ID NOs: 4025- 4391, or wherein the FcRn peptide has a sequence selected from any of SEQ ID NOs: 4392-4399. IgG Binding Moieties In certain embodiments, a half-life extension moiety is an IgG binding moiety. In certain embodiments, the IgG binding moiety is a peptide or a protein. In certain embodiments, the IgG binding moiety comprises no more than 10, no more than 11, no more than 12, no more than 13, no more than 14, no more than 15, no more than 16, no more than 17, no more than 18, no more than 19, no more than 20, no more than 21, no more than 22, no more than 23, no more than 24, or no more than 25 amino acids or amino acid mimetics. In certain embodiments, the IgG binding moiety comprises no more than 25, no more than 30, no more than 35, no more than 40, no more than 45, no more than 50, no more than 55, no more than 60, no more than 65, no more than 70, no more than 75, no more than 80, no more than 85, no more than 90, no more than 95, no more than 100, no more than 105, no more than 110, no more than 115, no more than 120, no more than 125, no more than 130, no more than 135, no more than 140, no more than 145, or no more than 150 amino acids or amino acid mimetics. In certain embodiments, the IgG binding moiety comprises 12-22 amino acids. In certain embodiments, the IgG binding moiety is a bicyclic peptide with a linear amino acid sequence comprising 12-22 linked amino acids. In certain embodiments, the IgG binding moiety comprises 105-140 amino acids. In certain embodiments, the IgG binding moiety is a VHH comprising 105- 140 amino acids. In certain embodiments, the IgG binding moiety is a peptide or protein with a molecular weight that is less than 15 kD, less than 14 kD, less than 13 kD, less than 12 kD, less than 11 kD, less than 10 kD, less than 9 kD, less than 8 kD, less than 7 kD, less than 6 kD, less than 5 kD, less than 4 kD, less than 3 kD, less than 2 kD, less than 1.5 kD, or less than 1 kD. In certain embodiments, the IgG binding moiety is a protein with a molecular weight of 12 kD-15 kD. In certain embodiments, the IgG binding moiety is a peptide with a molecular weight of less than 2 kD. In certain embodiments, the IgG binding moiety is a peptide with a molecular weight between 1 kD and 2 kD. Certain IgG binding moieties are provided in the table below. Table 5 Certain IgG Binding Moieties IgG IgG bindinSEQ ID In certain embodiments, IgG binding moieties are described in US 7,834,158; Sockolosky et al., PNAS, 2014; Fassina, et al, J. Biochem and Biophys Methods, 2001; Kabir, Immunol. Invest., 2002, Choe, et al., Materials, 2016; Muguruma, et al., ACS Omega, 2019. Certain Linkers In certain embodiments, complexes consist of macromolecules joined together by linkers In certain embodiments, complexes consist of macromolecules joined together by linkers and branching groups. In certain embodiments, the linker comprises a chain structure, such as a hydrocarbyl chain, or an oligomer of repeating units. In certain embodiments, the repeating unit is hydrophilic. In certain embodiments, the repeating unit is an ethylene oxide or a sarcosine. 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, a linker is absent and two moieties (e.g., a transferrin receptor binding moiety and an oligonucleotide) are joined by a single chemical bond. In certain embodiments, the linker comprises one or more functional groups described herein. In certain embodiments, linkers comprise 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, 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, a linker is introduced via an enzymatic reaction. In certain embodiments, a linker is introduced via 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 the linker comprises 10, 12, 14,16,18, 20, 22, 24, 26, 28, or 30 ethylene glycol units. In certain embodiments, the linker comprises 12 ethylene glycol units. In certain embodiments, the linker comprises 24 ethylene glycol units. A linker may comprise a cleavable moiety. Cleavable moieties include, but are not limited to, those which can be cleaved by enzymes, reducing conditions, or acidic conditions. A cleavable moiety may be stable outside the cell (e.g., in serum), but cleavable inside a cell. Examples of conditions leading to the cleavage of cleavable moieties include the addition of redox agents such as oxidative or reductive enzymes or reductive agents such as mercaptans; esterases; acidic media, for example, in lysosomes or endosomes (e.g., having a pH of six or lower); peptidases; nucleases; and phosphatases. In certain embodiments, a cleavable moiety is selectively cleavable 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 moiety is a phosphodiester. In certain embodiments, a cleavable moiety is 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 an oligonucleotide. In certain embodiments, a linker comprises a single cleavable moiety. In certain embodiments, a complex comprises a single cleavable moiety. In certain embodiments, a linker comprises 1-10 linker-nucleosides. Such linker-nucleosides may be linked by a phosphodiester internucleoside linkage to an adjacent nucleoside of an oligonucleotide. In certain embodiments, a linker-nucleoside comprises 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 oligomeric compound after it reaches a target tissue. Accordingly, linker-nucleosides are typically linked to one another and to the remainder of the oligonucleotide through cleavable linkages such as phosphodiester linkages and are cleavable in vivo. In certain embodiments, a linker comprises 2-5 linker-nucleosides. In certain embodiments, a linker comprises exactly 3 linker-nucleosides. In certain embodiments, a cleavable moiety comprises one or more 2′- deoxynucleoside. In certain such embodiments, the cleavable moiety comprises 2′-deoxyadenosine. In certain embodiments, a linker comprises a TCA trinucleotide. In certain embodiments, a cleavable moiety comprises a sugar such as a monosaccharide, disaccharide, or trisaccharide. In certain embodiments, a cleavable moiety is disclosed in WO 2018 / 136620, which is incorporated herein in the entirety. In certain embodiments, a linker comprises one or more functional groups selected from alkyl, amino, oxo, amide, disulfide, polyethylene glycol, ether, thioether, and hydroxylamino. In certain embodiments, a linker comprises chemical groups that are formed upon a reaction between a first functional group and a second functional group.. In certain embodiments, a first compound (e.g., a modified oligonucleotide) is attached to the first functional group during synthesis, and a second compound (e.g. a peptide) is attached to a second functional group during synthesis. Then, the two compounds are mixed under specific conditions to yield the linker. 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 azide-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, thioether 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, M., et al. Angew. Chem. Int. Ed.2021, 60 (21), 12109-12115; Dong, J., et al. Angew. Chem. Int. Ed.2014, 53 (36), 9430-9448.4; Zhang, C. et al. Angew. Chem. Int. Ed. Engl.2019, 58 (15), 4810–4839; Walsh, S. J., et al. Chem. Soc. Rev., 2021, 50, 1305-1353; Tiefenbrunn, T. et al. Biopolymers, 2010, 94 (1), 95-106; Drake, P. M., et al. Bioconjug. Chem.2014, 25 (7), 1331-1341; Bode, J. W., Acc. Chem. Res., 2017, 50 (9), 2104–2115; Magano, J., et al. Org. Proc. Res. Dev.2014, 18, 142-151; McKay, C. S. and Finn, M. G. Chem. Biol.2014, 21 (9), 1075-101; Christy, M. P. et al. Org. Lett.2020, 22, 2365; Ren, H., et al. Angew. Chem. Int. Ed. Engl. 2009, 48, 9658–9662; Rohrbacher, F. et al., Helv. Chim. Acta.2018, 101 (5), e1800039; Baalmaan, M., et al. Angew. Chem. Int. Ed.2020, 59 (31), 12885-12893; Lang, K., et al. J. Am. Chem. Soc.2014, 9 (1), 16-20; Nair, D. P., et al. Chem. Mater.201326 (1), 724-744; Kalia, J. and Raines, R. T. 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. In certain embodiments, a linker is formed 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, H. et al. J. Am. Chem. Soc.2012, 134(28), 11618- 11631, which is incorporated by reference herein in its entirety). Additional linkers suitable for oligonucleotide conjugates are prepared by Click chemistry described in “Click Chemistry for Biotechnology and Materials Science” Ed. Joerg Lahann, Wiley 2009, which is incorporated by reference herein in its entirety. Further examples of linking chemistry include an inverse electron demand Diels-Alder reaction, e.g., as described in Argamunt et al., J. Org. Chem.2020, 85, 10, 6593–6604, Sarrett et al., Nat. Protocols 2021, 16, 3348–3381; Handula et al., Molecules, 2021, 26 (15),),: 4640, Wiessler et al., Int. J. Med. Sci.2010,,; 7 (1),):, 19–28; copper-catalyzed azide-alkyne cycloaddition (CuAAC) see, e.g., S. I. Presolski, et al., J. Am. Chem. Soc.2010, 132, 14570–14576; D. Soriano Del Amo, et al., J. Am. Chem. Soc., 2010, 132, 16893– 16899; Staudinger reaction, see, e.g., Saxon and C. R. Bertozzi, Science, 2000, 287, 2007–2010; B. L. Nilsson, et al., Org. Lett., 2000, 2, 1939–1941, E. Saxon, et al., Org. Lett., 2000, 2, 2141–2143; formation of hydrazones and oximes, see, e.g., J. Y. Axup, et al., Proc. Natl. Acad. Sci. U. S. A., 2012, 109, 16101–16106; photoclick reactions, see, e.g., W. Song, et al., Angew. Chem., Int. Ed., 2008, 47, 2832–2835, A. Herner and Q. Lin, Top. Curr. Chem., 2016, 374, 1; strain-promoted alkyne-nitrone cycloaddition (SPANC) reactions, see, e.g., D. A. MacKenzie, et al., Curr. Opin. Chem. Biol., 2014, 21, 81–88; transition metal catalyzed cross coupling, see, e.g., M. Chalker, et al., J. Am. Chem. Soc., 2009, 131, 16346–16347; nucleophilic additions, in particular, of a thiol to a maleimide, see, e.g., Kang et al., Chem. Sci., 2021, 12, 13613-13647, Bernardim et al., Nat. Comm.2016, 7, 13128 (, 7, 13128, Jain et al., Pharmaceutical Research 2015, 32 (11), 3526-3540. In certain embodiments, the linker is prepared by reaction of a first reactive moiety with a second reactive moiety, wherein the first reactive moiety is attached to the oligonucleotide and the second reactive moiety is attached to the conjugate moiety, or a precursor thereof. In certain embodiments, the linker is prepared by reaction of a dipolarophile (e.g., a triple bonded moiety such as an alkyne or nitrile) with a 1,3- dipole (e.g., an azide, a nitrone, an isocyanate, or a thioisocyanate): wherein a carbon atom or a heteroatom, for example, one of X and Y is attached to a cargo as an and the other of X and Y is attached to a conjugate moiety such as a transferrin-receptor binding moiety or a half-life extension moiety. The linker thus prepared may comprise a five-membered unsaturated heterocyclic ring such as a triazole. In certain embodiments, the linker is prepared by reaction of a dieneophile (e.g., an electron rich double bond such as a furan or derivative thereof) with an electron poor diene (e.g., a tetrazine): a carbon atom or a heteroatom, for example, one of X and Y is attached to a cargo such as an oligonucleotide, and the other of X and Y is attached to a conjugate moiety such as a transferrin-receptor binding moiety or a half-life extension moiety. The linker thus prepared may comprise a six-membered unsaturated heterocyclic ring such as a dihydropyrazine. In certain embodiments, the linker is prepared by reaction of a nucleophile (e.g., a thiol or amine) with an electrophile (e.g., an electron-poor carbonyl or carbonyl-conjugated alkene or alkyne): wherein each Q is independently a carbon atom or a heteroatom, for example, one of X and Y is attached to a cargo such as an oligonucleotide, and the other of X and Y is attached to a conjugate moiety such as a transferrin-receptor binding moiety or a half-life extension moiety. The linker thus prepared may comprise a thioether, hydrazone, oxime, or amide. Each of the first reactive moiety and the second reactive moiety may attach at any suitable position of the cargo, the half-life extension moiety, and the transferrin-receptor binding moiety, for example, at a position described herein. In certain embodiments, the half-life extension moiety and / or the transferrin- receptor binding moiety comprises a peptide or polypeptide. In certain embodiments, the second reactive moiety is attached to an amino-acid side chain of the peptide or polypeptide. In certain embodiments, the second reactive moiety is attached to the N-terminus of the peptide or polypeptide. In certain embodiments, the second reactive moiety is attached to the C-terminus of the peptide or polypeptide. In certain embodiments, the second reactive moiety replaces the side-chain amino group of a lysine of a peptide or polypeptide. In certain embodiments, a linker has Formula L: [(RM1)-(RU)q1-(RM2)]q2L wherein each RM1 and RM2 is independently absent or a functional group derived from conjugation of a reactive moiety, for example wherein RM1 and RM2 are independently selected from an amino acid, O, NH, NRa2, S-S, O-NH, O-NRa2, NH-NH, NH-NRa2, NRa2-NRa2, C1-6haloalkylene, C2-6alkenylene, C2-6alkynylene, C3-10cycloalkylene, C6-10arylene, heteroarylene, heterocyclylene, C1-6alkylene-O-, C2-6alkenylene-O-, C2-6alkynylene-O-, C1-6alkylene-C(O)O, C1-6alkylene-NH, C1-6alkylene-NRa2, C1-6alkylene-C(O)NH, C1-6alkylene-C(O)NRa2, C(O), C(O)O, C(O)NH, C(O)NRa2, P(O)(OH), P(O)(NRa2), P(O)(SH), P(S)(NRa2), P(Ra2), P(NRa2), S, S(O)2, S(O), SRa2, and S(NRa2); each Ra2is independently selected from C(O)Ra3, C(O)ORa3, C(O)NHRa3, C(O)N(C1-4alkyl)Ra3, SRa3, S(O)2Ra3, S(O)Ra3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-10aryl, heteroaryl, and heterocyclyl; each Ra3is independently hydrogen, OH, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, heteroaryl, or heterocyclyl; and each RU is a repeating unit independently selected from C1-6alkylene, C1-6haloalkylene, C1-6heteroalkylene, C2-6alkenylene, C2-6alkynylene, C3-10cycloalkylene, C6-10arylene, heteroarylene, heterocyclylene, C1-6alkylene-O-, C2-6alkenylene-O-, C2-6alkynylene-O-, C1-6alkylene-C(O)O, C1-6alkylene-NH-, C1-6alkylene-NRa2-, C1-6alkylene-C(O)NH, C1-6alkylene-C(O)NRa2, a nucleotide, a saccharide, and an amino acid; and each RU is optionally substituted one with one, two, three, four, or five groups independently selected from halo (for example, fluoro), cyano, azido, OH, ORa2, NO2, NH2, NHRa2, N(Ra2)2, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-10aryl, heteroaryl, heterocyclyl, C1-6alkylene-ORa2, C2-6alkenylene-ORa2, C2-6alkynylene-ORa2, C1-6 alkylene-OH, C2-6alkenylene-OH, C2-6alkynylene-OH, C1- 6alkylene-NH2, C1-6alkylene-NHRa2, C1-6alkylene-N(Ra2)2, C(O)Ra3, C(O)ORa3, C(O)NHRa3, C(O)N(C1-4alkyl)Ra3, SRa3, S(O)2Ra3, S(O)Ra3, NHC(O)Ra3, N(C1-4alkyl)C(O)Ra3, NHS(O)Ra3, N(C1-4alkyl)S(O)Ra3, NHS(O)2Ra3, and N(C1-4alkyl)S(O)2Ra3; each Ra2is independently selected from C(O)Ra3, C(O)ORa3, C(O)NHRa3, C(O)N(C1-4alkyl)Ra3, SRa3, S(O)2Ra3, S(O)Ra3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-10aryl, heteroaryl, and heterocyclyl; each Ra3is independently hydrogen, OH, C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, heteroaryl, or heterocyclyl; or RU is a hydrophilic moiety; and wherein q1 is 0-30 and q2 is 1-20. In certain embodiments, an amino acid has a structure  (amino acid) wherein SC is an amino acid side chain found in a natural amino acid, and Ra4is H or Ra2as defined with respected to Formula L. In certain embodiments, SC is H or CH2OH. In certain embodiments, Ra2is methyl. In certain embodiments, a saccharide has a structure (saccharide) wherein Q1is OH, NH2, or NHAc are H and one of Q2attaches to the remainder of the linker. In certain embodiments, each RM1 and RM2 is independently selected from phosphate, diphosphate, triphosphate, phosphorothioate, phosphorodithioate, phosphorothiolate; phosphoramidates, alkylphosphonates, CH2-C(O)NH, O, NH, triazole, amide, carbonate, carbamate, urea, N- hydroxysuccinimide, oxime, hydrazone, disulfide, heteroaryl, heterocyclyl,

[0003] is In certain embodiments, each RM1 and RM2 is independently selected from P(O)(OH), O, CH2- C(O)NH , C(O)NH, or NH, and RU is ethylene glycol or CH2optionally substituted with C(O)OH or CH2OH. In certain embodiments, each RU is a hydrophilic moiety independently selected from (ethylene glycol)  (amino (sar), and CH2, wherein SC is an amino acid side chain, found in wherein CH2is optionally substituted as described above with respect to RU. In certain embodiments, each amino acid comprises a side chain found in a natural amino acid in its naturally occurring configuration. In certain embodiments, each RM1 and RM2 is independently selected from amino acid, C(O)NH, and heteroaryl, and RU is ethylene glycol or optionally substituted CH2. In certain embodiments, each RU is ethylene glycol or sar. In certain embodiments, each RU is ethylene glycol and q1 is 2-6. In certain embodiments, each RU is sar and q1 is 2-6. In certain embodiments, each RU is CH2and q1 is 1-6. In certain embodiments, RU is an amino acid, and SC is H or CH2OH. In certain embodiments, RU comprises glycine and / or serine. In certain embodiments, (RU)q1is (G3S)r1(SEQ ID NO: 199) or (G4S)r2, (SEQ ID NO: 200) wherein G is glycine and S is serine, and r1 and r2 are 1-5. In certain embodiments, (RU)q1is GGGS (SEQ ID NO: 201). In certain embodiments, each RU is an independently selected amino acid and (RU)q1is an amino acid sequence disclosed in US Patent No.7,612,181. In certain embodiments, (RU)q1is ASTKGP (SEQ ID NO: 202), or TVAAPSVFIFPP (SEQ ID NO: 203). In certain embodiments, (RU)q1is EPKSCDG4S (SEQ ID NO: 204), EPKSCD(G4S)2(SEQ ID NO:205) or EPKSCD(G4S)3(SEQ ID NO: 206). In certain embodiments, (RU)q1is Val-Cit, Gly-Val-Cit, or Gly-Gly-Gly. As a nonlimiting example, a linker L may be wherein RM1  -RM2  -RU-  RM1-  RU-  RM2 -  RM1-  -RM2  P(O)(OH)-  O-  (CH2)6-  C(O)NH-  OCH2-  heterocyclyl-  CH2- NH- e  , . . , d instances of RM1, RM2, and RU are absent. As a further nonlimiting example, a linker L may be wherein -RU- RM1-  RU-  RM2 -  l-  wherein heterocyclyl is a triazole fused (1R,8S)-bicyclo[6.1.0]non-4-ene, and unindicated instances of RM1, RM2, and RU are absent. Certain Branching Groups In certain embodiments, one or more linkers (for example, of Formula L) are joined by a branching group B. In certain embodiments, a branching group is a carbon atom, a nitrogen atom, a C3-10cycloalkyl, C6-10aryl, heteroaryl, or a heterocyclyl. In certain embodiments, a branching group has one of the following Formulas, for example, where each of X, Y, and Z is attached to one of a cargo such as an oligonucleotide, a transferrin-receptor binding moiety, and a half-life extension moiety, wherein each of X, Y, and Z is optionally attached through a linker: , In ce or . In certain embodiments, a linker has formula:   moiety and B is a branching group. In certain embodiments, a linker has formula:   is a half-life extension moiety and B is a branching group. In certain embodiments, a linker has formula: O H O X In certain embodiments, a linker has formula: wherein X is a transferrin-binding moiety and Y is a cargo. In certain embodiments, a linker has formula:   moiety and Y is a cargo. In certain embodiments, a linker has formula:   cargo. In certain embodiments, a linker comprises: In certain embodiments, a linker comprises: .  Certain C In certain embodiments, a Click reaction is used to form a linker by reacting: a terminal amine, including but not limited to the following compound: , to yield: , azide to yield: . following compound: . reaction is used to form a linker by reacting: in solution together with an but not limited to the following compound: , . the following compound: . In certain embodiments, a Click reaction is used to link a conjugate moiety and an oligonucleotide by reacting: wherein to the conjugate moiety and X is attached to the oligonucleotide, to yield: . a linker comprises: , 5  , , argo such as an oligomeric agent, a transferrin-receptor binding moiety, and a half-life extension moiety. Synthetic methods describing preparation of the above starting materials and intermediates can be found in one or more of the following: Agard, N. J., 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, K., and Chin, J. W. “Biorthogonal Reactions for Labeling Proteins.” ACS Chem. Biol. 2014, 9 (1), 16-20; Nair, D. P. 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; Kölmel, D. K. and Kool, E. T. “Oximes and Hydrazones in Bioconjugation: Mechanism and Catalysis.” Chem. Rev.2017, 117, 10358-10376; Wang, J. et al. “Polyfluorophenyl Ester-Terminated Homobifunctional Cross-Linkers for Protein Conjugation.” Synlett, 2017, 28 (15), 1934-1938; Kishimoto, S. et al. “Site-Specific Chemical Conjugation of Antibodies by Using Affinity Peptide for the Development of Therapeutic Antibody Format,” Bioconjugate Chem., 2019, 30 (3), 698-702, Wu and Devaraj, “Inverse Electron-Demand Diels–Alder Bioorthogonal Reactions,” Topics in Current Chemistry 2016, 374, 3, Oliveira et al., “Inverse electron demand Diels–Alder reactions in chemical biology,” Chem. Soc. Rev., 2017, 46, 4895-4950. Persons of skill in the art will appreciate that the identity of a linker in the context of a larger conjugate molecule may be interpretable in more than one manner. The present disclosure is intended to capture all such interpretations. For example, where a peptide described herein includes an N- or C-terminal extension, such extension may be interpreted as part of the bicyclic peptide, or as a short peptide part of a linker comprising such amino acids, as described herein. Additionally, a terminal atom or functional group of a half-life extension moiety, a transferrin-binding moiety, or a cargo may be drawn as a constituent of a linker or vice-versa. Generally, a complex described herein will not include a peroxide moiety (-O-O-).  Certain Complexes Provided herein are complexes comprising at least one half-life extension moiety, at least one transferrin receptor binding moiety, and at least one cargo. In certain embodiments, complexes further comprise one or more linker(s) and one or more branching group(s). In certain embodiments, the half-life extension moiety is selected from an albumin binding moiety, an FcRn binding moiety, and an IgG binding moiety. In certain embodiments, a complex comprises at least one half-life extension moiety, at least one transferrin receptor binding moiety, and at least one cargo. A cargo may be a single molecule or may be two or more molecules joined by non-covalent bonds. In certain embodiments, a 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, a cargo is a peptide, polypeptide, or protein. In certain embodiments, a cargo is a small molecule. In certain embodiments, the number of cargo attached to one half-life-extension moiety forms a ratio, which is the ratio of cargo per half-life-extension moiety. In certain embodiments, the ratio of the cargo to half-life-extension moiety 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 cargo to half-life-extension moiety is about 1 or greater. In some instances, the ratio the cargo to half-life-extension moiety is about 2 or greater. In some instances, the ratio of the cargo to half- life-extension moiety is about 3 or greater. In some instances, the ratio of the cargo to half-life-extension moiety is about 4 or greater. In some instances, the ratio of the cargo to half-life-extension moiety 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 cargo to half-life-extension moiety is 1. In some instances, the ratio of the cargo to half-life-extension moiety is 2. In some instances, the ratio of the cargo to half-life-extension moiety is 4. In certain embodiments, the number of transferrin receptor binding moieties associated with one half-life extension moiety forms a ratio, which is the ratio of cell-targeting moieties per half-life extension moiety. In certain embodiments, a transferrin receptor binding moiety is covalently attached to a half-life extension moiety. In these embodiments, the ratio of transferrin receptor binding moieties to half-life extension moieties 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 transferrin receptor binding moiety to half-life extension moiety is about 1 or greater. In some instances, the ratio of the transferrin receptor binding moiety to the half-life extension moiety is about 2 or greater. In some instances, the ratio of the transferrin receptor binding moiety to half-life extension moiety is about 3 or greater. In some instances, the ratio of the transferrin receptor binding moiety to the half-life extension moiety is about 4 or greater. In some instances, the ratio of the transferrin receptor binding moiety to the half-life extension moiety 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 transferrin receptor binding moiety to the half-life extension moiety is 1. In some instances, the ratio of the transferrin receptor binding moiety to the half-life extension moiety is 2. In certain embodiments, the number of transferrin receptor binding moieties associated with one cargo forms a ratio, which is the ratio of transferrin receptor binding moieties per cargo. In certain embodiments, the ratio of transferrin receptor binding moieties to cargo 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 moiety to cargo is about 0.5 or lower. In some instances, the ratio of the transferrin receptor binding moiety to cargo is about 1 or lower. In some instances, the ratio of the transferrin receptor binding moiety to cargo is about 1 or greater. In some instances, the ratio of the transferrin receptor binding moiety to cargo is about 2 or greater. In some instances, the ratio of the transferrin receptor binding moiety to cargo is about 3 or greater. In some instances, the ratio of the transferrin receptor binding moiety to cargo is about 4 or greater. In some instances, the ratio of the transferrin receptor binding moiety to cargo 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 the transferrin receptor binding moiety to cargo is 0.5. In some instances, the ratio of the transferrin receptor binding moiety to cargo is 1. In some instances, the ratio of the transferrin receptor binding moiety to cargo is 2. In certain embodiments, the complex is capable of interacting with the type 1 transferrin receptor. In certain embodiments, the 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 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 complex does not cause dimerization of the type 1 transferrin receptor. In certain embodiments, a complex is capable of being internalized when it interacts with or binds the transferrin receptor. In certain embodiments, a complex is capable of delivering cargo to a cell when it interacts with or binds the transferrin receptor. In certain embodiments, the half-life extension moiety is covalently attached to the transferrin receptor binding moiety, optionally via a linker. In certain embodiments, the half-life extension moiety is a peptide or protein. In certain embodiments, the transferrin receptor binding moiety is attached at the N- terminus or C-terminus of the peptidic half-life extension moiety. In certain embodiments, the transferrin receptor binding moiety is attached through a side chain of the peptidic half-life extension moiety. In certain embodiments, the transferrin receptor binding moiety is a peptide or protein. In certain embodiments, the half-life extension moiety is attached at the N-terminus or C-terminus of the peptidic transferrin receptor binding moiety. In certain embodiments, the half-life extension moiety is attached through a side chain of the peptidic transferrin receptor binding moiety. In certain embodiments, a transferrin receptor binding moiety and a half-life extension moiety are different regions of a single N-to-C linked polypeptide. In certain embodiments, the cargo is covalently attached to the half-life extension moiety, optionally via a linker. In certain embodiments, the half-life extension moiety is a peptide or protein. In certain embodiments, the cargo is attached at the N-terminus or C-terminus of the peptidic half-life extension moiety. In certain embodiments, the cargo is attached through a side chain of the peptidic half-life extension moiety. In certain embodiments, the transferrin receptor binding moiety is a peptide or protein. In certain embodiments, the cargo is attached at the N-terminus or C-terminus of the peptidic transferrin receptor binding moiety. In certain embodiments, the cargo is attached through a side chain of the peptidic transferrin receptor binding moiety. In certain embodiments, each of the half-life extension moiety, the transferrin receptor binding moiety, and the cargo attach to a branching group, optionally via linker(s). In certain embodiments, the cargo is attached to the half-life extension moiety, optionally through a linker. In certain embodiments, the complex can be represented by any one of the following formulae: A‐L1‐T‐L2‐C  T‐L1‐A‐L2‐C  C‐L1‐T‐L2‐A  C‐L1‐A‐L2‐T  A‐L1‐C‐L2‐T  T‐L1‐C‐L2‐A  A—L1     B—L2—C                  an life extension moiety; T represents a transferrin-receptor binding moiety, C represents a cargo; each of L1, L2, and L3represents an independently selected linker; and B is a branching group. In certain embodiments, the complex is represented by A—L1     moiety; T is a transferrin-receptor binding moiety; C is a cargo; L1 is a linker; L2a L3a linker comprising a polyethylene glycol having 10, 12, 14,16,18, 20, 22, 24, 26, 28, or 30 ethylene glycol units, and B is a branching group. In certain such embodiments, T is a transferrin binding bicycle ligand. In certain embodiments, T is BCY17995 or B191. In certain such embodiments, A is an albumin binding moiety. In certain embodiments, A is selected from SA21 and . In certain embodiments, L1is .  embodiments, L2is .  ; wherein n is from 10 to 30. In certain embodiments, provided is a complex comprising an oligomeric agent, at least one half-life extension moiety selected from a peptide and a lipid, and at least one transferrin-receptor binding moiety, optionally wherein the transferrin-receptor binding moiety is a bicyclic peptide; and wherein the complex does not comprise an Fc domain; wherein the oligomeric agent comprises a first modified oligonucleotide duplexed with a second compound that is represented by one of the following formulae:  A‐L1‐X‐L2‐T  T‐L1‐X‐L2‐A  wherein A represents the half-life extension moiety; T represents the transferrin-receptor binding moiety, and X represents a second modified oligonucleotide (from 5’ to 3’); each of L1and L2represent an independently selected linker or optionally is absent. In certain embodiments, the oligomeric agent is an RNAi agent, the first modified oligonucleotide is an antisense RNAi oligonucleotide, and the second modified oligonucleotide is a sense RNAi oligonucleotide. In certain embodiments, the half-life extension moiety is a peptide with a molecular weight of 1-500 Da, 500 Da-1 kD, 500 Da-1.5 kD, 500 Da-2 kD, 1 kD-2 kD, 1 kD-1.5 kD, or 1.5 kD-2 kD. In certain embodiments, the half-life extension moiety comprises one or two fatty acids. In certain embodiments, the half-life tain attached at a non-terminal nucleoside of X and L1is optionally absent. In certain embodiments, provided is a complex comprising an oligomeric agent, at least one albumin- binding moiety having a linear amino acid sequence with at least 80%, at least 90%, at least 95%, or 100% identity any of SEQ ID NOs: 266, or 267, and at least one transferrin-receptor binding moiety, wherein the transferrin-receptor binding moiety is a bicyclic peptide having a linear amino acid sequence having at least 80%, at least 90%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 2, 3, 21-29, or 31- 191; and wherein the complex does not comprise an Fc domain; wherein the oligomeric agent comprises an antisense RNAi compound comprising or consisting of an antisense RNAi oligonucleotide duplexed with a sense RNAi compound comprising a sense RNAi oligonucleotide that is represented by one of the following formulae:  A‐L1‐X‐L2‐T  T‐L1‐X‐L2‐A  wherein A represents the half-life extension moiety; T represents the transferrin-receptor binding moiety, and X represents the sense RNAi oligonucleotide (from 5’ to 3’); each of L1and L2represent an independently selected linker. In certain embodiments, the transferrin-receptor binding moiety is a bicyclic peptide having a linear amino acid sequence having at least 80%, at least 90%, at least 90%, at least 95%, or 100% identity to SEQ ID NO: 3, 26, 81, 82, 83, 84, or 85. In certain embodiments, the transferrin-receptor binding moiety is a bicyclic peptide having a linear amino acid sequence having at least 80%, at least 90%, at least 90%, at least 95%, or 100% identity to SEQ ID NO: 3. In certain embodiments, the transferrin-receptor binding moiety is a bicyclic peptide having a linear amino acid sequence having at least 80%, at least 90%, at least 90%, at least 95%, or 100% identity to SEQ ID NO: 26, and optionally having a N-terminal extension comprising 1-5 amino acids and / or a C-terminal extension comprising 1-5 amino acids. In certain embodiments, the transferrin-receptor binding moiety is a bicyclic peptide having a linear amino acid sequence having at least 80%, at least 90%, at least 90%, at least 95%, or 100% identity to SEQ ID NO: 26, and optionally having a C-terminal extension EPW. In certain embodiments, the bicyclic peptide is a bicycle ligand on a TATB molecular scaffold. In certain embodiments, the albumin-binding moiety is a peptide having a linear amino acid sequence having at least 80%, at least 90%, at least 90%, at least 95%, or 100% identity to SEQ ID NO: 267. In certain embodiments, the combined molecular weight of A+T+L1+L2+L3+B is less than 50 kD, less than 45 kD, less than 40 kD, less than 35 kD, less than 30 kD, less than 25 kD, less than 20 kD, less than 15 kD, less than 10 kD, less than 5 kD, less than 4 kD, less than 3 kD, or less than 2 kD. In certain embodiments, the combined molecular weight of the complex is less than 50 kD, less than 45 kD, less than 40 kD, less than 35 kD, less than 30 kD, less than 25 kD, less than 20 kD, less than 15 kD, less than 10 kD, less than 5 kD, less than 4 kD, less than 3 kD, or less than 2 kD. In certain embodiments, the complex has a total molecular weight of 1 kD to 50 kD, 5 kD to 50 kD, 5 kD to 40 kD, 5 kD to 30 kD, 5 kD to 20 kD, 10 kD to 50 kD, 10 kD to 40 kD, 10 kD to 30 kD, 10 kD to 20 kD, or 15 kD to 25 kD. Oligomeric Agents as Cargo In certain embodiments, the cargo is an oligomeric agent comprising a modified oligonucleotide. In certain such embodiments, the modified oligonucleotide is covalently attached to the half-life extension moiety, optionally through a linker. In certain embodiments, the half-life extension moiety is a peptide or protein. In certain embodiments, the modified oligonucleotide is covalently attached to the N-terminus or C- terminus of the peptidic half-life extension moiety. In certain embodiments, the oligomeric compound is covalently attached through a side chain of the peptidic half-life extension moiety. In certain embodiments, the 5’-end of the modified oligonucleotide is attached to the half-life extension moiety. In certain embodiments, the 3’-end of the modified oligonucleotide is attached to the half-life extension moiety. In certain embodiments, the modified oligonucleotide and the half-life extension moiety are attached through click chemistry. In certain embodiments, the modified oligonucleotide is covalently attached to the transferrin receptor binding moiety, optionally through a linker. In certain embodiments, the transferrin receptor binding moiety is a peptide or protein. . In certain embodiments, the modified oligonucleotide is covalently attached to the transferrin receptor binding moiety through an amino acid side-chain. In certain embodiments, the oligomeric compound is covalently attached to the N-terminus or C-terminus of the transferrin receptor binding moiety. In certain embodiments, the modified oligonucleotide is covalently attached to the transferrin receptor binding moiety through an amino acid side-chain. In certain embodiments, the modified oligonucleotide and the transferrin receptor binding moiety are attached through click chemistry. In certain embodiments, the oligomeric agent is an oligomeric duplex comprising an antisense oligonucleotide and a sense oligonucleotide. In certain embodiments, the half-life extension moiety is a peptide or protein. In certain embodiments, the antisense oligonucleotide is covalently attached to the half- life extension moiety via an amino acid side-chain, optionally through a linker. In certain embodiments, the antisense oligonucleotide is covalently attached to the N-terminus or C-terminus of the half-life extension moiety, optionally through a linker. In certain embodiments, the 5’-end of the antisense oligonucleotide is attached to the half-life extension moiety. In certain embodiments, the 3’-end of the antisense oligonucleotide is attached to the half-life extension moiety. In certain embodiments, the sense oligonucleotide is covalently attached to the half-life extension moiety via an amino acid side-chain, optionally through a linker. In certain embodiments, the sense oligonucleotide is covalently attached to the N-terminus or C-terminus of the half- life extension moiety, optionally through a linker. In certain embodiments, the 5’-end of the sense oligonucleotide is attached to the half-life extension moiety. In certain embodiments, the 3’-end of the sense oligonucleotide is attached to the half-life extension moiety. In certain embodiments, the antisense oligonucleotide is covalently attached to a transferrin receptor binding moiety, optionally through a linker. In certain embodiments, the transferrin receptor binding moiety is a peptide or protein In certain such embodiments, the antisense oligonucleotide is covalently attached to the transferrin receptor binding moiety through the N-terminus or C-terminus, optionally through a linker. In certain embodiments, the antisense oligonucleotide is covalently attached to the transferrin receptor binding moiety through an amino acid side-chain, optionally through a linker. In certain embodiments, the sense oligonucleotide is covalently attached to a transferrin receptor binding moiety, optionally through a linker. In certain embodiments, the transferrin receptor binding moiety is a peptide or protein In certain such embodiments, the sense oligonucleotide is covalently attached to the transferrin receptor binding moiety through the N-terminus or C-terminus, optionally through a linker. In certain embodiments, the sense oligonucleotide is covalently attached to the transferrin receptor binding moiety through a side-chain, optionally through a linker. In certain embodiments, the 5’-end of the sense oligonucleotide is attached to the transferrin receptor binding moiety. In certain embodiments, the 3’-end of the sense oligonucleotide is attached to the transferrin receptor binding moiety. Peptides or Proteins as Cargo In certain embodiments, the cargo is a peptide, polypeptide, or protein (a ‘peptidic cargo’). In certain such embodiments, the peptidic cargo is covalently attached to the half-life extension moiety, optionally through a linker. In certain embodiments, the half-life extension moiety is a peptide or protein. In certain embodiments, the peptidic cargo is covalently attached to the N-terminus or C-terminus of the peptidic half- life extension moiety. In certain embodiments, the peptidic cargo is covalently attached through a side chain of the peptidic half-life extension moiety. In certain embodiments, the N-terminus of the peptidic cargo is attached to the half-life extension moiety. In certain embodiments, the C-terminus of the peptidic cargo is attached to the half-life extension moiety. In certain embodiments, a side-chain of the peptidic cargo is attached to the half-life extension moiety. In certain embodiments, the peptidic cargo is covalently attached to the transferrin receptor binding moiety, optionally through a linker. In certain embodiments, the transferrin receptor binding moiety is a peptide or protein. In certain embodiments, the peptidic cargo is covalently attached to the N-terminus or C- terminus of the transferrin receptor binding moiety. In certain embodiments, the peptidic cargo is covalently attached through a side chain of the peptidic transferrin receptor binding moiety. In certain embodiments, the N-terminus of the peptidic cargo is attached to the transferrin receptor binding moiety In certain embodiments, the C-terminus of the peptidic cargo is attached to the transferrin receptor binding moiety. In certain embodiments, a side-chain of the peptidic cargo is attached to the transferrin receptor binding moiety. Small Molecules as Cargo In certain embodiments, the cargo is a small molecule, such as a fluorophore or an active drug substance. In certain such embodiments, the small molecule is covalently attached to the half-life extension moiety, optionally through a linker. In certain embodiments, the half-life extension moiety is a peptide or protein. In certain embodiments, the small molecule is covalently attached to the N-terminus or C-terminus of the peptidic half-life extension moiety. In certain embodiments, the small molecule is covalently attached through a side chain of the peptidic half-life extension moiety. In certain embodiments, the small molecule is covalently attached to the transferrin receptor binding moiety, optionally through a linker. In certain embodiments, the transferrin receptor binding moiety is a peptide or protein. In certain embodiments, the small molecule is covalently attached to the N-terminus or C- terminus of the transferrin receptor binding moiety. In certain embodiments, the small molecule is covalently attached through a side chain of the peptidic transferrin receptor binding moiety. Certain Oligonucleotides In certain embodiments, provided herein are complexes comprising oligomeric agents comprising oligomeric compounds comprising oligonucleotides, 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 In certain embodiments, modified sugar moieties are non-bicyclic modified sugar moieties. In certain embodiments, modified sugar moieties are bicyclic or tricyclic sugar moieties. In certain embodiments, modified sugar moieties are sugar surrogates. Such sugar surrogates may comprise one or more substitutions corresponding to those of other types of modified sugar moieties. In certain embodiments, modified sugar moieties are non-bicyclic modified furanosyl sugar moieties comprising one or more acyclic substituent, including, but not limited to, substituents at the 2’, 3’, 4’, and / or 5’ positions. In certain embodiments, the furanosyl sugar moiety is a ribosyl sugar moiety. In certain embodiments, one or more acyclic substituent of non-bicyclic modified sugar moieties is branched. In certain embodiments, non-bicyclic modified sugar moieties comprise a substituent group at the 2’- position. Examples of substituent groups suitable for the 2’-position of modified sugar moieties include but are not limited to: -F, -OCH3(“OMe” or “O-methyl”), and -OCH2CH2OCH3(“MOE”). In certain embodiments, 2’-substituent groups are selected from 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) Mol Canc Ther 6(3):833-843; Grunweller, A. et al., (2003) Nucleic Acids Research 31(12):3185- 3193). Herein, general descriptions of bicyclic nucleosides include both isomeric configurations. When the positions of specific bicyclic nucleosides (e.g., LNA or cEt) are identified in exemplified embodiments herein, they are in the β-D configuration, unless otherwise specified. In certain embodiments, modified sugar moieties comprise one or more non-bridging sugar substituent and one or more bridging sugar substituent (e.g., 5’-substituted and 4’-2’ bridged sugars). In certain embodiments, modified sugar moieties are sugar surrogates. In certain such embodiments, the oxygen atom of the sugar moiety is replaced, e.g., with a sulfur, carbon or nitrogen atom. In certain such embodiments, such modified sugar moieties also comprise bridging and / or non-bridging substituents as described herein. For example, certain sugar surrogates comprise a 4’-sulfur atom and a substitution at the 2'- position and / or the 5’ position. In certain embodiments, sugar surrogates comprise rings having other than 5 atoms. For example, in certain embodiments, a sugar surrogate comprises a six-membered tetrahydropyran (“THP”). Such tetrahydropyrans may be further modified or substituted. Nucleosides comprising such modified tetrahydropyrans include, but are not limited to, hexitol nucleic acid (“HNA”), anitol nucleic acid (“ANA”), manitol nucleic acid (“MNA”), fluoro HNA: (“F-HNA”, see e.g., Elgi, et. al., J Am Chem (2011) 133(41):16642-16649, Swayze et al., U.S.8,088,904; and Swayze et al., U.S.8,440,803) F-HNA can also be referred to as a F-THP or 3'-fluoro tetrahydropyran, and nucleosides comprising additional modified THP compounds having the formula: wherein, independently, for each of said modified THP nucleoside: Bx is a nucleobase moiety; T3and T4are each, independently, an internucleoside linking group linking the modified THP nucleoside to the remainder of an oligonucleotide or one of T3and T4is an internucleoside linking group linking the modified THP nucleoside to the remainder of an oligonucleotide and the other of T3and T4is H, a hydroxyl protecting group, a linker, or a 5' or 3'-terminal group; q1, q2, q3, q4, q5, q6and q7are each, independently, H, C1-C6alkyl, substituted C1-C6alkyl, C2-C6alkenyl, substituted C2-C6alkenyl, C2-C6alkynyl, or substituted C2-C6alkynyl; and each of R1and R2is independently selected from among: hydrogen, halogen, substituted or unsubstituted alkoxy, NJ1J2, SJ1, N3, OC(=X)J1, OC(=X)NJ1J2, NJ3C(=X)NJ1J2, and CN, wherein X is O, S or NJ1, and each J1, J2, and J3is, independently, H or C1-C6alkyl. In certain embodiments, modified THP nucleosides are provided wherein q1, q2, q3, q4, q5, q6and q7are each H. In certain embodiments, at least one of q1, q2, q3, q4, q5, q6and q7is other than H. In certain embodiments, at least one of q1, q2, q3, q4, q5, q6and q7is methyl. In certain embodiments, modified THP nucleosides are provided wherein one of R1and R2is F. In certain embodiments, R1is F and R2is H, in certain embodiments, R1is methoxy and R2is H, and in certain embodiments, R1is methoxyethoxy and R2is H. In certain embodiments, sugar surrogates comprise rings having more than 5 atoms and more than one heteroatom. For example, nucleosides comprising morpholino sugar moieties and their use in oligonucleotides have been reported. As used here, the term “morpholino” means a sugar surrogate having the following structure: O OBx. morpholinos may be modified, for example, by adding or altering various substituent groups from the above morpholino structure. Such sugar surrogates are referred to herein as “modified morpholinos.” In certain embodiments, sugar surrogates comprise acyclic moieties. Examples of nucleosides and oligonucleotides comprising such acyclic sugar surrogates include, but are not limited to: peptide nucleic acid (“PNA”), acyclic butyl nucleic acid ), and nucleosides and oligonucleotides described in Manoharan et al., U.S.10,913,767. Representative U.S. patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Patent Nos.5,539,082; 5,714,331; and 5,719,262. In certain embodiments, sugar surrogates are the “unlocked” sugar structure of UNA (unlocked nucleic acid) nucleosides. UNA is a nucleoside wherein any of the bonds of the sugar moiety has been removed, forming an unlocked sugar surrogate. A representative U.S. publication that teaches the preparation of UNA includes, but is not limited to, US Patent Publication No 2011 / 0313020.

[0004] In certain embodiments, sugar surrogates are the glycerol as found in GNA (glycol nucleic acid) nucleosides as depicted below: (S)-GNA any nucleobase. bicyclic and tricyclic sugar and sugar surrogates are known in the art that can be used in modified nucleosides. 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), 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): 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): from O or S, R4Cis N(Ra)(Rb); R5Cis selected from H, OH, halogen, O-C1-C12 alkyl, alkyl, C1-C12alkyl , substituted C1-C12alkyl, C1-C12alkenyl, substituted C1-C12alkenyl; Raand Rbare independently selected from H, C1-C6alkyl, substituted C1-C6alkyl, C1-C6alkenyl, substituted C1-C6alkenyl, acetyl, formyl, or together form a 5-7-membered heterocycle; excluding where X is O, R4Cis NH2and R5Cis H (unmodified cytosine). In certain embodiments, modified nucleobases are selected from: 5-substituted pyrimidines, 6- azapyrimidines, alkyl or alkynyl substituted pyrimidines, alkyl substituted purines, and N-2, N-6 and O-6 substituted purines. In certain embodiments, modified nucleobases are selected from: 5-methylcytosine, 2- aminopropyladenine, 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-N- methylguanine, 6-N-methyladenine, 2-propyladenine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5- propynyl (-C ^C-CH3) uracil, 5-propynylcytosine, 6-azouracil, 6-azocytosine, 6-azothymine, 5-ribosyluracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl, 8-aza and other 8-substituted purines, 5-halo (particularly 5-bromo), 5-trifluoromethyl, 5-halouracil, and 5-halocytosine, 7-methylguanine, 7-methyladenine, 2-F-adenine, 2-aminoadenine, 7-deazaguanine, 7-deazaadenine, 3-deazaguanine, 3- deazaadenine, 6-N-benzoyladenine, 2-N-isobutyrylguanine, 4-N-benzoylcytosine, 4-N-benzoyluracil, 5- methyl 4-N-benzoylcytosine, 5-methyl 4-N-benzoyluracil, universal bases, hydrophobic bases, promiscuous bases, size-expanded bases, and fluorinated bases. Further modified nucleobases include tricyclic pyrimidines, such as 1,3-diazaphenoxazine-2-one, 1,3-diazaphenothiazine-2-one and 9-(2-aminoethoxy)-1,3- diazaphenoxazine-2-one (G-clamp). Modified nucleobases may also include those in which the purine or pyrimidine base is replaced with other heterocycles, for example 7-deaza-adenine, 7-deazaguanosine, 2- aminopyridine and 2-pyridone. Further nucleobases include those disclosed in Englisch et al., Angewandte Chemie, International Edition, 1991, 30, 613; Sanghvi, Y.S., Chapter 15, Antisense Research and Applications, Crooke, S.T. and Lebleu, B., Eds., CRC Press, 1993, 273-288; and those disclosed in Chapters 6 and 15, Antisense Drug Technology, Crooke S.T., Ed., CRC Press, 2008, 163-166 and 442-443. Publications that teach the preparation of certain of the above noted modified nucleobases, as well as other modified nucleobases include without limitation, Rogers et al., U.S.5,134,066 ; Benner et al., U.S. 5,432,272; Matteucci et al., U.S.5,502,177 ; Froehler et al., U.S.5,594,121 ; and Cook et al., U.S.5,681,941. 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 such internucleoside linking group of a modified oligonucleotide: X is selected from O or S; R1is selected from H, C1-C6alkyl, and substituted C1-C6alkyl; and T is selected from SO2R2, C(=O)R3, and P(=O)R4R5, wherein: R2is selected from an aryl, a substituted aryl, a heterocycle, a substituted heterocycle, an aromatic heterocycle, a substituted aromatic heterocycle, a diazole, a substituted diazole, a C1-C6alkoxy, C1-C6alkyl, C1-C6alkenyl, C1-C6alkynyl, substituted C1-C6alkyl, substituted C1-C6alkenyl substituted C1-C6alkynyl, and a 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 is any of those described in WO2016 / 028187, incorporated by reference herein. In certain embodiments, a modified internucleoside linkage comprises the formula: ;  for each such internucleoside linking group of a modified oligonucleotide: O, S, Se, C1-4alkyl, NH, BH3; R1and R2are independently selected from H, NR1AR1B, OR3, SR3, S(O)H, S(O)R3, S(O)2H, S(O)2R3, S(O)2NH2, S(O)2NHR3, S(O)2N(R3)2, C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, C6-C10aryl; or R wherein each R1A, R1B, R2A, and R2Bis independently selected from H, C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, or C6-C10aryl; and R3is selected from C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, or C6-C10aryl. In certain embodiments, a modified internucleoside linkage comprises a modified linking group having a formula: ;   internucleoside linking group of a modified oligonucleotide: Z is selected from O, S, Se, C1-4alkyl, NH, BH3; R1, R2, R3, and R4are each independently selected from H, C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, or C6-C10aryl; or R1and R3are each C(J)2and together form a 5-membered ring and / or R2and R4are each C(J)2and together form a 5-membered ring; or R1and R2are each C(J)2and together form a 5-membered ring; wherein J is selected from H, C1-C10alkyl, C2-C10alkenyl, C2-C10alkynyl, or C6-C10aryl. In certain embodiments, a modified internucleoside linkage comprises a linking group having a formula: . a modified internucleoside linkage comprises a mesyl phosphoramidate linking group having a formula: In certain internucleoside linkage may comprise a chiral center. In certain 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: 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.

[0005] 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. In certain embodiments, each nucleoside of a uniformly modified comprises a 2’- MOE. In certain embodiments, each nucleoside of a uniformly modified comprises a 2’-NMA. In certain embodiments, the modified oligonucleotide comprises or consists of 14-20 contiguous modified nucleosides comprising a modified sugar moiety, wherein each modified sugar moiety is independently selected from 2’- MOE, 2’-NMA, 2’-OMe, LNA, and cEt. In certain embodiments, the modified oligonucleotide comprises or consists of 14-20 contiguous modified nucleosides comprising a modified sugar moiety, wherein each modified sugar moiety is independently selected from 2’-MOE and 2’-NMA. In certain embodiments, an RNAse H agent comprises a first modified oligonucleotide and a second modified oligonucleotide complementary to the first modified oligonucleotide. Such agents are described in, for example, WO2019 / 118916, WO2013 / 089283, WO2018 / 062510, Yoshioka et al., Nucleic Acids Research, 2019, Vol.47, No.147321–32, Ono et al., Molecular Therapy: Nucleic Acids, 2021, Vol.23, 1360-70. 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-propynepyrimidine. 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 embodiments, the above modifications (sugar, nucleobase, internucleoside linkage) are incorporated into a modified oligonucleotide. In certain embodiments, modified oligonucleotides are characterized by their modification motifs and overall lengths. In certain embodiments, such parameters are each independent of one another. Thus, unless otherwise indicated, each internucleoside linkage of an oligonucleotide having a gapmer sugar motif may be modified or unmodified and may or may not follow the gapmer modification pattern of the sugar modifications. For example, the internucleoside linkages within the wing regions of a sugar gapmer may be the same or different from one another and may be the same or different from the internucleoside linkages of the gap region of the sugar motif. Likewise, such sugar gapmer oligonucleotides may comprise one or more modified nucleobase independent of the gapmer pattern of the sugar modifications. Unless otherwise indicated, all modifications are independent of nucleobase sequence. 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, an oligomeric compound described herein comprises an oligonucleotide having a nucleobase sequence complementary to that of a target nucleic acid. In certain embodiments, an oligomeric compound is paired with a second oligomeric compound to form an oligomeric duplex. Thus, in certain embodiments, an oligomeric agent is an oligomeric duplex. Such oligomeric duplexes comprise a first oligomeric compound having a region complementary to a target nucleic acid and a second oligomeric compound having a region complementary to the first oligomeric compound. In certain embodiments, the first oligomeric compound 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 oligomeric compound of an oligomeric duplex comprises or consists essentially of a modified or unmodified oligonucleotide. In certain embodiments, the second oligomeric compound 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 oligomeric compounds of an oligomeric duplex may comprise a linker and / or a terminal group. The oligonucleotides of each oligomeric compound 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 oligomeric compound of an oligomeric duplex comprises or consists essentially of a modified or unmodified oligonucleotide and a transferrin-receptor binding moiety or a half- life extension moiety, and optionally a linker. In certain embodiments, the second oligomeric compound of an oligomeric duplex comprises or consists essentially of a modified or unmodified oligonucleotide and a transferrin-receptor binding moiety or a half-life extension moiety, and optionally a linker. In certain embodiments, the first oligomeric compound is an antisense compound. In certain embodiments, the first modified oligonucleotide is an antisense oligonucleotide. In certain embodiments, the second oligomeric compound is a sense compound. 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 certain embodiments, the oligomeric agent comprises a first oligomeric compound and a second oligomeric compound, wherein the first oligomeric compound comprises or consists essentially of a modified or unmodified oligonucleotide and a transferrin-receptor binding moiety or a half-life extension moiety, and optionally a linker, and the second oligomeric compound comprises or consists essentially of a modified or unmodified oligonucleotide and a transferrin-receptor binding moiety or a half-life extension moiety, and optionally a linker, wherein the first oligomeric compound and the second oligomeric compound form an oligomeric duplex. In certain embodiments, the oligomeric agent comprises a first oligomeric compound and a second oligomeric compound, wherein the first oligomeric compound comprises or consists essentially of an antisense RNAi oligonucleotide and a transferrin-receptor binding moiety or a half-life extension moiety, and optionally a linker, and the second oligomeric compound comprises or consists essentially of a sense RNAi oligonucleotide and a transferrin-receptor binding moiety or a half-life extension moiety, and optionally a linker, wherein the first oligomeric compound and the second oligomeric compound form an oligomeric duplex. 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 certain embodiments, the oligomeric agent is an RNAi agent and comprises a 2’-OMe or a 2’- MOE nucleoside at position 1 from the 5’-terminus of the antisense RNAi oligonucleotide. In certain embodiments, the antisense RNAi oligonucleotide comprises a stabilized phosphate group at the 5’-most nucleoside. In certain embodiments, the stabilized phosphate group is an (E)-vinyl phosphonate. In certain embodiments, the oligomeric agent is an RNAi agent and one, two, or three of the nucleosides at positions 3, 4, and 5 from the 5’-terminus of the antisense RNAi oligonucleotide are 2’-OMe nucleosides. In certain embodiments, the oligomeric agent is an RNAi agent and each of the nucleosides at positions 3, 4, and 5 from the 5’-terminus of the antisense RNAi oligonucleotide are 2’-OMe nucleosides. In certain embodiments, the oligomeric agent is an RNAi agent and one, two, three, four, or five of the nucleosides at positions 7, 8, 9, 10, and 11 from the 5’-terminus of the antisense RNAi oligonucleotide are 2’-OMe nucleosides. In certain embodiments, the oligomeric agent is an RNAi agent and one, two, three, four, or five of the nucleosides at positions 17, 18, 19, 20, and 21 from the 5’-terminus of the antisense RNAi oligonucleotide are 2’-OMe nucleosides. In certain embodiments, the oligomeric agent is an RNAi agent and each of the nucleosides at positions 17, 18, 19, 20, and 21 from the 5’-terminus of the antisense RNAi oligonucleotide are 2’-OMe nucleosides. In certain embodiments, the oligomeric agent is an RNAi agent and one, two, three, or four of the nucleosides at positions 2, 6, 14, and 16 from the 5’-terminus of the antisense RNAi oligonucleotide are 2’-F nucleosides. In certain embodiments, the oligomeric agent is an RNAi agent and each nucleoside in the sense RNAi oligonucleotide is independently selected from: a bicyclic nucleoside, a 2’-OMe nucleoside, a 2’-F nucleoside, a 2’-MOE nucleoside, a 2’-NMA nucleoside, a 2’-deoxynucleoside, and a ribosyl nucleoside. In certain embodiments, the oligomeric agent is an RNAi agent and at least one of the nucleosides at positions 3-6 and 8 from the 5’-terminus of the sense RNAi oligonucleotide are 2’-OMe nucleosides, optionally wherein each of the nucleosides at positions 3-6 and 8 is a 2’-OMe nucleoside. In certain embodiments, the oligomeric agent is an RNAi agent and at least one of the nucleosides at positions 12-19 from the 5’-terminus of the sense RNAi oligonucleotide are 2’-OMe nucleosides, optionally wherein each of the nucleosides at positions 12-19 is a 2’-OMe nucleoside. In certain embodiments, the oligomeric agent is an RNAi agent and one, two, three, or four of the nucleosides at positions 7 and 9-11 from the 5’-terminus of the sense RNAi oligonucleotide are 2’-F nucleosides, optionally wherein each of the nucleosides at positions 7 and 9-11 is a 2’-F nucleoside. 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 oligomeric compound can comprise a stabilized phosphate group at the 5’ position of the 5’-most nucleoside. In any of the oligomeric duplexes described herein, the first oligomeric compound can comprise a stabilized phosphate group attached to the 5’ position of the 5’-most nucleoside. In certain embodiments, an antisense RNAi oligonucleotide comprises a stabilized phosphate group at the 5’-most nucleoside. In certain embodiments, the stabilized phosphate group comprises a cyclopropyl phosphonate or an (E)-vinyl phosphonate. In certain embodiments, the stabilized phosphate group is an (E)-vinyl phosphonate. Certain stabilized phosphates are described in WO2010 / 048585, WO2010 / 048549, WO 2011 / 139702, WO 2017 / 214112, WO 2018 / 045317, and WO 2024 / 062413. In certain embodiments, the stabilized phosphate group has a structure , moiety, optionally to the 4’-position of.furanosyl sugar moiety, and wherein Re1and Re2are independently selected from hydrogen, halo (for example, fluoro), OH, O-C1-6alkyl, NH2, NHC1-6alkyl, N(C1-6alkyl)2, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, and C2-6alkynyl, and wherein Ring E is a 3-4 membered cycloalkyl ring optionally substituted with 1-4 groups independently selected from halo (for example, fluoro), OH, O-C1-6alkyl, NH2, NHC1-6alkyl, N(C1-6alkyl)2, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, and C2-6alkynyl. 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 oligomeric compound and / or the second oligomeric compound can comprise a linker connected to a half-life extension moiety, a transferrin receptor binding moiety, or another molecule. In certain embodiments, an oligomeric compound comprises exactly one linker. In certain embodiments, an oligomeric compound comprises exactly two linkers. In certain embodiments, an oligomeric compound comprises 0, 1, 2, 3, or 4 linkers. In certain embodiments, an oligomeric compound comprises one linker to a half-life extension moiety. In certain embodiments, an oligomeric compound comprises one linker to a transferrin receptor binding moiety. In alternative embodiments, an oligomeric compound comprises two linkers attached at distinct parts of the modified oligonucleotide, wherein one linker connects to a half-life extension moiety, and the second linker connects to transferrin receptor binding moiety. 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 transferrin receptor binding moiety. In certain embodiments, the linker connects to a half-life extension moiety. In certain embodiments, the first modified oligonucleotide is connected to a linker that connects to a half-life extension moiety, and the second modified oligonucleotide is connected to a linker that connects to a transferrin receptor binding moiety. In certain embodiments, the first modified oligonucleotide is connected to a linker that connects to a transferrin receptor binding moiety, and the second modified oligonucleotide is connected to a linker that connects to a half-life extension moiety. In certain such embodiments, the cell- targeting moiety is a transferrin receptor binding moiety. In certain embodiments, the first modified oligonucleotide is an RNase H oligonucleotide. In certain embodiments, the first modified oligonucleotide comprises a deoxy region. In certain embodiments, each nucleoside of the deoxy region comprises a 2’-β-D-deoxyribosyl sugar moiety. In certain embodiments, the first modified oligonucleotide comprises a deoxy region consisting 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, the first modified oligonucleotide comprises a deoxy region flanked on its 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. In certain embodiments, the first modified oligonucleotide consists of the 5’-region, the deoxy region, and the 3’-region in a contiguous sequence of nucleosides. In certain embodiments, each nucleoside of the 5’-region and each nucleoside of the 3’-region of the first modified oligonucleotide comprises a modified sugar moiety. In certain embodiments, the nucleosides within the 5’-region each 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 of the first modified oligonucleotide comprises at least one nucleoside comprising a 2’-substituted sugar moiety. In certain embodiments, the 5’-region of the first modified oligonucleotide comprises at least one nucleoside comprising a bicyclic sugar moiety. In certain embodiments, the 3’-region of the first modified oligonucleotide comprises at least one nucleoside comprising a 2’-substituted sugar moiety. In certain embodiments, the 3’-region of the first modified oligonucleotide comprises at least one nucleoside comprising a bicyclic sugar moiety. In certain embodiments, the 5’-region and the 3’-region of the first modified oligonucleotide each comprises 1-8 nucleosides. In certain embodiments, the 5’-region of the first modified oligonucleotide comprises 1-7 nucleosides. In certain embodiments, the 5’-region of the first modified oligonucleotide comprises 1-6 nucleosides. In certain embodiments, the 5’-region of the first modified oligonucleotide comprises 1, 2, 3, 4, 5, 6, 7, or 8 nucleosides. In certain embodiments, the 3’-region of the first modified oligonucleotide comprises 1-7 nucleosides. In certain embodiments, the 3’-region of the first modified oligonucleotide comprises 1-6 nucleosides. In certain embodiments, the 3’-region of the first modified oligonucleotide comprises 1, 2, 3, 4, 5, 6, 7, or 8 nucleosides. In certain embodiments, the first modified oligonucleotide comprises or consists of 16-20 linked nucleosides. In certain embodiments, the first modified oligonucleotide is a 3-10-3 BNA gapmer, a 3-10-3 cEt gapmer, a 3-10-3 LNA gapmer, or a 5-10-5 MOE gapmer. In certain embodiments, the first modified oligonucleotide comprises a deoxy region and 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%, 95%, or 100% complementary to the nucleobase sequence of an equal portion of the first modified oligonucleotide. In certain embodiments, the second modified oligonucleotide comprises 9-20 linked nucleosides. In certain embodiments, the second modified oligonucleotide comprises at least one nucleoside comprising a 2’-OMe sugar moiety. In certain embodiments, the second modified oligonucleotide comprises 1-16 nucleosides comprising a 2’-OMe sugar moiety. In certain embodiments, the second modified oligonucleotide comprises at least one nucleoside comprising a bicyclic sugar moiety. In certain embodiments, the second modified oligonucleotide comprises 1-6 nucleosides comprising a bicyclic sugar moiety. In certain embodiments, the second modified oligonucleotide comprises at least one nucleoside comprising a 2’-deoxy sugar moiety. In certain embodiments, the second modified oligonucleotide comprises 1-16 nucleosides comprising a 2’-deoxy sugar moiety. In certain embodiment, the oligomeric agent comprises a first modified oligonucleotide and a second modified oligonucleotide, wherein the first modified oligonucleotide comprises a deoxy region and the transferrin-receptor binding moiety is attached at the 3’-end or the 5’-end of the first modified oligonucleotide; and the half-life extension moiety is attached at the 3’-end or the 5’-end of the second modified oligonucleotide. In certain embodiments, the complex does not comprise an Fc polypeptide. In certain embodiments, the Fc polypeptide does not comprise a cell-targeting moiety. In certain embodiments, the Fc polypeptide does not comprise a transferrin-receptor binding moiety. Antisense Activity In certain embodiments, oligomeric compounds and oligomeric duplexes are capable of hybridizing to a target nucleic acid, resulting in at least one antisense activity; such oligomeric compounds and oligomeric duplexes are antisense compounds. In certain embodiments, antisense compounds 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 compounds selectively affect one or more target nucleic acid. Such antisense compounds comprise a nucleobase sequence that hybridizes to one or more target nucleic acid, resulting in one or more desired antisense activity and does not hybridize to one or more non-target nucleic acid or does not hybridize to one or more non-target nucleic acid in such a way that results in significant undesired antisense activity. In certain antisense activities, hybridization of an antisense compound to a target nucleic acid results in recruitment of a protein that cleaves the target nucleic acid. For example, certain antisense compounds result in RNase H mediated cleavage of the target nucleic acid. RNase H is a cellular endonuclease that cleaves the RNA strand of an RNA:DNA duplex. The DNA in such an RNA:DNA duplex need not be unmodified DNA. In certain embodiments, antisense compounds described herein are sufficiently “DNA- like” to elicit RNase H activity. In certain embodiments, one or more non-DNA-like nucleoside in the gap of a gapmer is tolerated. In certain antisense activities, an antisense compound or a portion of an antisense compound is loaded into an RNA-induced silencing complex (RISC), ultimately resulting in cleavage of the target nucleic acid. For example, certain antisense compounds result in cleavage of the target nucleic acid by Argonaute. Antisense compounds that are loaded into RISC are RNAi compounds. RNAi compounds may be double- stranded (siRNA) or single-stranded (ssRNA). In certain embodiments, hybridization of an antisense compound to a target nucleic acid does not result in recruitment of a protein that cleaves that target nucleic acid. In certain embodiments, hybridization of the antisense compound to the target nucleic acid results in alteration of splicing of the target nucleic acid. In certain embodiments, hybridization of an antisense compound to a target nucleic acid results in inhibition of a binding interaction between the target nucleic acid and a protein or other nucleic acid. In certain embodiments, hybridization of an antisense compound to a target nucleic acid results in alteration of translation of the target nucleic acid. Antisense activities may be observed directly or indirectly. In certain embodiments, observation or detection of an antisense activity involves observation or detection of a change in an amount of a target nucleic acid or protein encoded by such target nucleic acid, a change in the ratio of splice variants of a nucleic acid or protein and / or a phenotypic change in a cell or subject. Certain Target Nucleic Acids In certain embodiments, oligomeric compounds 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., half-life extension moieties, transferrin receptor binding moieties) 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. Alternatively, a nucleic acid molecule encoding protein 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 embodiments, an expression vector comprising the nucleotide sequence of a protein 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 protein. In specific embodiments, the expression of the protein 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 a protein described herein. Such host-expression systems represent vehicles by which the coding sequences of the protein is produced and subsequently purified, but also represent cells that are, when transformed or transfected with the appropriate nucleotide coding sequences, express a protein 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 protein 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 a protein 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 any protein. In some instances, a number of selection systems are used, including but not limited to the herpes simplex virus thymidine kinase (Wigler et ak, 1977, Cell 11:223), hypoxanthine- guanine phosphoribosyltransferase (Szybalska & Szybalski, 192, Proc. Natl. Acad. Sci. USA 48:202), and adenine phosphoribosyltransferase (Lowy et ak, 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 ak, 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, J. Mol. Biol.150:1). In some instances, the expression levels of a protein 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 protein, production of the protein 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 proteins 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, a target nucleic acid is expressed in muscle tissue. In certain embodiments, a target nucleic acid is expressed in cardiac tissue. In certain embodiments, a target nucleic acid is expressed in peripheral nerve tissue. In certain embodiments, the target nucleic acid is selected from APP, ASPA, ATXN1, ATXN2, ATXN3, CD20, CLN3, CLN7, DARS2, DMD, DMPK, GFAP, FUS, GYS1, IFNAR1, KCNT1, LRRK2, HTT, MeCP2, PRNP, PLP1, SCN1A, SCN2A, SMN2, SNCA, SOD1, STMN2, TAU / MAPT, TECPR2, TREM2, TTR, TUG1, and UBE3A. Certain Pharmaceutical Compositions In certain embodiments, a 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 complex, for example, by infusion or subcutaneous injection. In certain embodiments, pharmaceutical compositions disclosed herein are prepared for oral administration. In certain embodiments, pharmaceutical compositions are prepared for buccal administration. In certain embodiments, a pharmaceutical composition is prepared for administration by injection (e.g., intravenous, subcutaneous, intramuscular, intrathecal (IT), intracerebroventricular (ICV), etc.). In certain embodiments, a pharmaceutical composition is prepared for administration by intravenous injection. In certain of such embodiments, a pharmaceutical composition comprises a carrier and is formulated in aqueous solution, such as water or physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer. In certain embodiments, other ingredients are included (e.g., ingredients that aid in solubility or serve as preservatives). In certain embodiments, injectable suspensions are prepared using appropriate liquid carriers, suspending agents and the like. Certain pharmaceutical compositions for injection are presented in unit dosage form, e.g., in ampoules or in multi-dose containers. Certain pharmaceutical compositions for injection are suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or dispersing agents. Certain solvents suitable for use in pharmaceutical compositions for injection include, but are not limited to, lipophilic solvents and fatty oils, such as sesame oil, synthetic fatty acid esters, such as ethyl oleate or triglycerides, and liposomes. Aqueous injection suspensions may contain any of the above excipients. Under certain conditions, certain oligomeric compounds 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, tautomeric forms, resonance structures and / or as salts in equilibrium with protonated or ionic forms. Drawn structures are intended to capture all such forms of such compounds. With respect to linkers, all stereoisomers of chemical compounds are encompassed by a chemical structure, even if the structure is drawn with a particular (relative or absolute) stereochemical configuration. 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 compound 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 of modified oligonucleotides targeted to mouse MALAT1, conjugated at the 5′ end Modified oligonucleotides targeted to mouse MALAT1 were prepared using standard techniques, then further modified at the 5′ end. The modified oligonucleotides in the table below are 16 nucleotides in length and are 3-10-3 cEt gapmers with uniform phosphorothioate internucleoside linkages. The modified oligonucleotides have a nucleobase sequence of (from 5′ to 3′): GCATTCTAATAGCAGC (SEQ ID NO: 1), wherein each cytosine is a 5- methylcytosine, and are complementary to mouse MALAT1. Compound No.722061 has a 6-aminohexyl phosphoryl linker conjugated at the 5′ end. Compound No.1639301 has a 6-(BCN-carbamate)hexyl phosphoryl linker conjugated at the 5′ end. Compound No.556089 and Compound No.722061 were previously disclosed in WO 2017 / 192820. Compound No.1639301 was synthesized from Compound No. 722061, as described below. Table 6 3-10-3 cEt gapmers with uniform phosphorothioate internucleoside linkages targeted to mouse MALAT1 SEQ Compound Sequence (5′ to 3′)Sugar Motif Internucleoside Linker at 5′ ID moiety, each “s” represents a phosphorothioate internucleoside linkage, and each cytosine is a 5- methylcytosine. Preparation of Compound No.1639301 Compound No.1639301, having a 6-(BCN-carbamate)hexyl linker attached via a phosphodiester group at the 5′ end of the modified oligonucleotide, was prepared from Compound No.722061. To a solution of Compound No.722061 (16 µmol, 90 mg) dissolved in 600 μL of 0.1 M borax buffer, pH 8.5 was added a solution of BCN-NHS ester (3 eq., 48 µmol, 14 mg) dissolved in DMF (500 µL). The reaction mixture was stirred for 2 h at room temperature, then purified by ion-exchange HPLC 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 and lyophilized to give Compound No. 1639301 (9.7 µmol, 61% yield). Example 2: Conjugation of transferrin receptor binding moieties and albumin-binding moieties to modified oligonucleotides Transferrin receptor binding moieties and albumin-binding moieties were designed by conjugating a TfR1-binding moiety to an albumin-binding moiety. The TfR1 and albumin-binding moieties were then conjugated to a modified oligonucleotide at the 5′ end. Conjugated peptides comprising a TfR1-binding moiety linked to an albumin-binding moiety were procured from WuXi AppTec. The TfR1-binding moiety is bicycle ligand BCY17995 or B191. A PEG linker is attached at the C-terminus of the bicycle ligand, and the other end of the PEG linker is attached to a 6-azido-L-lysine. BCY17901, the parent bicycle ligand for BCY17995, was previously disclosed in International Patent Publ. WO 2023 / 056388. The albumin-binding moiety is cyclic peptide SA21, with a L- propargyl glycine residue inserted at the N-terminus, and a 6-(2-azidoacetyl)-L-lysine substituted for the first lysine residue. The amino acid sequences of the binding moieties are described in the table below. Each sequence in the table below is acetylated at the N-terminus and amidated at the C-terminus. Peptide SA21- alkyne is cyclized via disulfide bond between the two cysteines at positions 10 and 16. B191 and BCY17995 are bicyclized on a TATB scaffold via thioether bonds to the three cysteine residues at positions 1, 9, and 13, as shown below: . Table 7 Amino acid sequences of TfR1-binding moieties and albumin-binding moiety SEQ Compound Binding C-terminal In the table above, [HyP] represents 4-trans-hydroxy-L-proline; [tBuGly] represents t-butyl glycine; [K(N3)] represents 6-azido-L-lysine; [Prg] represents L-propargyl glycine; [K(N3Gly)] represents a 6-(2-azidoacetyl)- L-lysine; [PEG12] represents an amino-PEG12 carboxylic acid linker; [PEG24] represents an amino-PEG24 carboxylic acid linker. The TfR1 binding moiety was attached to the albumin binding moiety via a SPAAC reaction between the C- terminal 6-azido-L-lysine residue of the bicycle ligand and the N-terminal L-propargyl glycine residue of the SA21-alkyne, following procedures described in Angelini et al. J. Med. Chem.2012, 55(22), 10187-10197. The sequences of the Tfr1 and albumin-binding moieties are provided in the table below. Each sequence in the table below is acetylated at the N-terminal cysteine and the L-propargyl glycine; and amidated at the C- terminal aspartic acid and the 6-azido-L-lysine. The albumin-binding moiety is cyclized by a disulfide bridge between its two cysteine residues. The TfR1-binding moiety is bicyclized on a TATB scaffold via thioether bonds to its three cysteine residues, as shown below: . Table 8 Sequences of TfR1 and albumin-binding moieties BCY-SA21 TfR1 binding moiety SEQ Linker Albumin binding moiety SEQ Com ound Amino Acid Se uence ID NO Amino Acid Se uence ID NO represents 6-azido-L-lysine; [Prg] represents L-propargylglycine; [K(N3Gly)] represents a 6-(2-azidoacetyl)- L-lysine; [PEG12] represents an amino-PEG12 carboxylic acid linker; [PEG24] represents an amino-PEG24 carboxylic acid linker. Conjugation of a TfR1 and albumin-binding moiety to a modified oligonucleotide A solution of Compound No.1639301 (12.2 mg, 2.11 µmol, 1 eq.) dissolved in sterile water (0.5 mL) was mixed with a solution of B191-PEG24-SA21 (17.34 mg, 3.17 µmol, 1.5 eq.) in DMF (0.5 mL). The reaction mixture was shaken at room temperature for 18 hours, with reaction monitoring by LC-MS. After completion, the reaction mixture was diluted with water (30 mL) and purified by strong anion exchange (SAX) HPLC using a Waters Source 30Q (2.54 × 8 cm) column in a gradient of 0 to 60% Buffer B (1.5 M NaBr, 100 mM NH4OAc in 30% aq. acetonitrile) in Buffer A (100 mM NH4OAc in 30% aq. acetonitrile). Fractions containing the purified product were pooled and concentrated, then desalted by RP-HPLC on a Transgenomics Oligo S8 C18 column (2 × 16 cm, 9 µm), washing with 0.1 M NaCl, then water. The purified compound was eluted in 50% aq. Acetonitrile and concentrated to yield purified Compound No.1820496 (15.3 mg, 1.35 µmol, 64% yield). Compound No.1820682 (15.3 mg, 1.4 µmol, 62% yield) was synthesized from Compound No.1639301 (13 mg, 2.25 µmol, 1 eq.) and BCY17995-PEG12-SA21 (18.5 mg, 3.38 µmol, 1.5 eq.) in the same manner as described above. Example 3: Activity of complexes comprising a modified oligonucleotides targeting mouse Malat1 in hTfR+ / -transgenic mice Complexes Compound No.1820496 and Compound No.1820682 comprising transferrin receptor bicycle ligands, SA21, and modified oligonucleotides complementary to mouse MALAT1 described in the above examples were analyzed for their effects on mouse Malat1 in hTfR+ / -transgenic mice. Human transferrin receptor (hTFR) / CD71 knock-in mice used in these studies 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(SEQ ID NO: 211). 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)(SEQ ID NO: 212) and NM_001128148.2 (human)(SEQ ID NO: 211). 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 hTfR+ / -transgenic mice herein. 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. hTfR+ / -transgenic mice were divided into groups of 4 mice each. Each mouse received intravenous injections of complexes comprising modified oligonucleotides conjugated to either B191 or BCY17995 and an albumin binding moiety once a week for 4 weeks for a total of 4 treatments (on Days 1, 8, 15, and 22) at various doses indicated in the table below. One group of 4 mice received intravenous injections of PBS once a week for 4 weeks (a total of 4 treatments). The PBS-injected group served as the control group. 2 weeks post final treatment (Day 36), mice were sacrificed and RNA was extracted from olfactory bulb, spinal cord, and various mouse brain tissues (cortical brain tissue, striatum, cerebellum, thalamus, hippocampus, and brain stem) for real-time RTPCR analysis of mouse Malat1 RNA expression. Mouse Malat1 primer probe set mMalat1#2 (forward sequence TGGGTTAGAGAAGGCGTGTACTG, designated herein as SEQ ID NO: 11; reverse sequence TCAGCGGCAACTGGGAAA, designated herein as SEQ ID NO: 12; probe sequence CGTTGGCACGACACCTTCAGGGACT, designated herein as SEQ ID NO: 13) was used to measure mouse Malat1 RNA levels. Malat1 RNA levels were normalized to mouse GAPDH. Mouse GAPDH was amplified using primer probe set mGapdh_LTS00102 (forward sequence GGCAAATTCAACGGCACAGT, designated herein as SEQ ID NO: 14; reverse sequence GGGTCTCGCTCCTGGAAGAT, designated herein as SEQ ID NO: 15; probe sequence AAGGCCGAGAATGGGAAGCTTGTCATC, designated herein as SEQ ID NO: 16). Results are presented as percent Malat1 RNA, relative to the amount of Malat1 in PBS treated animals (%control).

[0006] Table 9 Reduction of mouse Malat1 RNA by complexes comprising a transferrin receptor binding moiety and an albumin binding moiety in hTfR+ / -transgenic mice Malat1 RNA (% control) Compound Dose Spinal Brain Olfactory Example 4: Design and synthesis of transferrin receptor binding moieties conjugated to albumin binding moieties Preparation of bicycle peptide B192 . Bicycle peptide B192, shown above, was synthesized using standard Fmoc chemistry. B192 has the linear sequence: CP[HyP]DAHLGC[tBuGly]SYCEPWK (SEQ ID NO: 5), wherein [Hyp] is L- hydroxyproline, and [tBuGly] is t-butyl glycine; and wherein the peptide is acetylated at the N-terminus and amidated at the C-terminus. The title compound was synthesized using standard Fmoc chemistry. Rink amide MBHA resin (0.5 mmol, 1 eq., 0.3 mmol / g, 1.67 g resin) in DMF was agitated under N2for 2 hours at 20 °C, then filtered to collect the resin. For each step of the peptide synthesis, sequential deprotection followed by coupling was performed using the following conditions: Fmoc Deprotection Conditions: 20% piperidine in DMF (50 mL) was added to the resin and agitated under N2for 15 min. The resin was washed with DMF (50 mL × 5) and filtered to isolate the resin. Peptide Coupling Conditions: A solution of Fmoc-Lys(Dde)-OH (1.5 eq.), diisopropylethylamine (DIEA) (3.0 eq.) and HATU (1.425 eq.) in DMF (15.0 mL) was added to the resin and agitated under N2for 30 min at 20 °C. The resin was then washed with DMF (50 mL × 5). The deprotection / coupling sequence was repeated with the following amino acids: Fmoc-Trp(Boc)- OH, Fmoc-Pro-OH, Fmoc-Glu(OtBu)-OH, Fmoc-Cys(Trt)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Ser(tBu)-OH, Fmoc-tBuGly-OH, Fmoc-Cys(Trt)-OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-His(Trt)-OH, Fmoc-Ala-OH, Fmoc-Asp(OtBu)-OH, Fmoc-HyP-OH, Fmoc-Pro-OH and Fmoc-Cys(Trt)-OH. Following peptide synthesis, the N-terminus of the peptide was acetylated by treating the resin with acetic anhydride (3 eq.) and DIEA (4 eq.) for 15 mins. The resin was then washed with DMF (50ml × 5). To remove the lysine protecting group, 3% hydrazine in DMF (50 mL) was added and the resin was agitated under N2for another 15 mins. The resin was washed with DMF (50 mL × 5) and filtered. Fmoc-NH-PEG2-CH2COOH was coupled to the peptide then deprotected following the coupling / deprotection conditions described above. Coupling and deprotection was repeated with a second portion of Fmoc-NH-PEG2-CH2COOH, then Fmoc-g-Glu-OH, and finally 18-(tert-butoxy)-18-oxooctade...

Claims

Claims 1. A complex, comprising at least one cargo, at least one half-life extension moiety, and at least one transferrin-receptor binding moiety; wherein the transferrin-receptor binding moiety does not comprise an scFv domain; and wherein the complex does not comprise an Fc domain.

2. The complex of claim 1, wherein at least one transferrin-receptor binding moiety is covalently attached to at least one half-life extension moiety, optionally through a linker.

3. The complex of claim 1 or 2, wherein at least one transferrin-receptor binding moiety is covalently attached to at least one cargo, optionally through a linker.

4. The complex of any of claims 1-3, wherein at least one half-life extension moiety is covalently attached to at least one cargo, optionally through a linker.

5. The complex of any of claims 1-4, comprising exactly one transferrin-receptor binding moiety.

6. The complex of any of claims 1-5, wherein the transferrin-receptor binding moiety is selected from a peptide or protein.

7. The complex of claim 6, wherein the transferrin-receptor binding moiety is a linear peptide, a cyclic peptide, or a bicyclic peptide.

8. The complex of claim 7, wherein the transferrin-receptor binding moiety comprises a bicyclic peptide with a linear amino acid sequence having at least 80%, at least 90%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 2, 3, 21-29, or 31-191.

9. The complex of claim 6, wherein the transferrin-receptor binding moiety is a VNAR or a VHH.

10. The complex of any of claims 6-9, wherein the half-life extension moiety is attached at the N- terminus of the transferrin-receptor binding moiety, optionally through a linker.

11. The complex of any of claims 6-9, wherein the half-life extension moiety is attached at the C- terminus of the transferrin-receptor binding moiety, optionally through a linker.

12. The complex of any of claims 6-9, wherein the half-life extension moiety is attached through a side chain of the transferrin-receptor binding moiety, optionally through a linker.

13. The complex of any of claims 6-12, wherein the cargo is attached at the N-terminus of the transferrin- receptor binding moiety, optionally through a linker.

14. The complex of any of claims 6-12, wherein the cargo is attached at the C-terminus of the transferrin- receptor binding moiety, optionally through a linker.

15. The complex of any of claims 6-12, wherein the cargo is attached through a side chain of the transferrin-receptor binding moiety, optionally through a linker.

16. The complex of any of claims 1-15, comprising exactly one half-life extension moiety.

17. The complex of any of claims 1-15, comprising exactly two half-life extension moieties.

18. The complex of any of claims 1-17, wherein the half-life extension moiety is an albumin-binding moiety, an FcRn-binding moiety, or an IgG-binding moiety.

19. The complex of claim 18, wherein the half-life extension moiety is an albumin-binding moiety.

20. The complex of claim 19, wherein the albumin-binding moiety is a fatty acid.

21. The complex of claim 20, wherein the albumin-binding moiety comprises: . 22.

23. terminus of the half-life extension moiety, optionally through a linker.

24. The complex of claim 22, wherein the transferrin-receptor binding moiety is attached at the C- terminus of the half-life extension moiety, optionally through a linker.

25. The complex of claim 22, wherein the transferrin-receptor binding moiety is attached through a side chain of the half-life extension moiety, optionally through a linker.

26. The complex of any of claims 22-25, wherein the cargo is attached at the N-terminus of the half-life extension moiety, optionally through a linker.

27. The complex of any of claims 22-25, wherein the cargo is attached at the C-terminus of the half-life extension moiety, optionally through a linker.

28. The complex of any of claims 22-25, wherein the cargo is attached through a side chain of half-life extension moiety, optionally through a linker.

29. The complex of any of claims 22-28, wherein the half-life extension moiety is an albumin-binding peptide.

30. The complex of claim 29, wherein the albumin binding peptide has a linear amino acid sequence with at least 80%, at least 90%, at least 95%, or 100% identity any of SEQ ID NOs: 4, 266, or 267.

31. The complex of claim any of claims 18 or 22-28, wherein the half-life extension moiety is an FcRn- binding moiety.

32. The complex of claim 31, wherein the FcRn-binding moiety is a peptide.

33. The complex of claim 32, wherein the peptide has a linear amino acid sequence having at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 277 or 278.

34. The complex of any of claims 1-33, wherein at least one linker comprises a hydrophilic moiety.

35. The complex of claim 34, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine.

36. The complex of claim 35, wherein at least one linker comprises a PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24.

37. The complex of claim 35, wherein at least one linker comprises (sarcosine)n, where is n is 1 to 10.

38. The complex of any of claims 1-37, wherein the cargo is selected from an oligomeric agent, a small molecule, a peptide, a protein, or a fluorophore.

39. The complex of any of claims 1-38, wherein the wherein the complex is represented by one of the following formulae: A‐L1‐T‐L2‐C  T‐L1‐A‐L2‐C  C‐L1‐T‐L2‐A  C‐L1‐A‐L2‐T  A‐L1‐C‐L2‐T  T‐L1‐C‐L2‐A;  wherein A represents a half-life extension moiety; T represents a transferrin-receptor binding moiety, C represents a cargo; each of L1and L2is an independently selected linker.

40. The complex of any of claims 1-38, wherein the complex is represented by one of the following formulae: A—L1     B—L2—C         L1—A  C—L2—B   wherein A represents an half-life extension moiety; T represents a transferrin-receptor binding moiety, C represents a cargo; each of L1, L2, and L3represents an independently selected linker; and B is a branching group.

41. The complex of claim 39 or 40, wherein at least one linker comprises a hydrophilic moiety.

42. The complex of claim 41, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine.

43. The complex of any of claims 39-41, wherein L1comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24.

44. The complex of any of claims 39-43, wherein L1comprises (sarcosine)n, where is n is 1 to 10.

45. The complex of any of claims 39-44, wherein L2comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24.

46. The complex of any of claims 39-44, wherein L2comprises (sarcosine)n, where is n is 1 to 10.

47. The complex of any of claims 40-46, wherein L3comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24.

48. The complex of any of claims 40-46, wherein L3comprises (sarcosine)n, where is n is 1 to 10.

49. The complex of any of claims 40-48, wherein B is a branching group selected and.

50. of any of claims 39-49, wherein the transferrin-receptor binding moiety is a peptide or a51. The complex of claim 50, wherein the transferrin-receptor binding moiety is a linear peptide, a cyclic peptide, or a bicyclic peptide.

52. The complex of claim 51, wherein the transferrin-receptor binding moiety is a bicyclic peptide with a linear amino acid sequence having at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 2, 3, 21-29, or 31-191.

53. The complex of claim 51, wherein the transferrin-receptor binding moiety is a VNAR or a VHH.

54. The complex of any of claims 39-53, wherein the half-life extension moiety is an albumin-binding moiety, an FcRn-binding moiety, or an IgG-binding moiety.

55. The complex of claim 54, wherein the half-life extension moiety is an albumin-binding moiety.

56. The complex of claim 55, wherein the albumin-binding moiety is a fatty acid.

57. The complex of claim 56, wherein the albumin-binding moiety comprises: .

59. The complex of claim 55, wherein the peptide has a linear amino acid sequence with at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 4, 266, or 267.

60. The complex of claim 54, wherein the half-life extension moiety is an FcRn-binding moiety.

61. The complex of claim 60, wherein the FcRn-binding moiety is a peptide.

62. The complex of claim 60, wherein the peptide has a linear amino acid sequence having at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 277 or 278.

63. The complex of any of claims 1-62, wherein the complex consists of a cargo and the structure:, wherein n is 10-30.

64. The complex of claim 30, wherein the albumin binding peptide is SA21 (SEQ ID NO.: 266) or ABDCon (SEQ ID NO.: 267).

65. The complex of claim 64, wherein the half-life extension moiety is attached through a linker.

66. The complex of claim 65, wherein the linker comprises an N-terminal G[Ac-K-heterocyclyl], wherein [Ac-K- .

67. The complex of claim 20,is or 68.

69. The complex of claim 68, wherein the linker comprises a hydrophilic moiety.

70. The complex of claim 69, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine.

71. The complex of claim 70, wherein the linker comprises a PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24.

72. The complex of claim 71, wherein the linker .

73. The complex of claim 71 or 72, wherein the linker is.has a molecular weight that is less than 15 kD, less than 14 kD, less than 13 kD, less than 12 kD, less than 11 kD, less than 10 kD, less than 9 kD, less than 8 kD, less than 7 kD, less than 6 kD, less than 5 kD, less than 4 kD, less than 3 kD, less than 2 kD, less than 1.5 kD, or less than 1 kD.

76. The complex of claim 75, wherein the transferrin receptor binding moiety is a protein with a molecular weight of 12 kD-15 kD.

77. The complex of claim 64, wherein the transferrin receptor binding moiety is a peptide with a molecular weight of 500 Da-1 kD, 500 Da-1.5 kD, 500 Da-2 kD, 1 kD-2 kD, 1 kD-1.5 kD, or 1.5 kD- 2 kD.

78. The complex of claim 77, wherein the transferrin receptor binding moiety is a bicyclic peptide having a total molecular weight including scaffold of 500 Da-1 kD, 500 Da-1.5 kD, 500 Da-2 kD, 1 kD-2 kD, 1 kD-1.5 kD, or 1.5 kD-2 kD.

79. The complex of claim 75, wherein the transferrin receptor binding moiety is a protein comprising 105-140 amino acids.

80. The complex of claim 75, wherein the transferrin receptor binding moiety is a peptide comprising or consisting of 8-22, 10-22, 10-20, 10-18, 10-16, 12-16, 12-18, 12-20, 12-22, 14-22, 14-16, 14-18, 14- 20, 16-20 linked amino acids.

81. The complex of any of claims 1-80, wherein the half-life extension moiety has a molecular weight that is less than 15 kD, less than 14 kD, less than 13 kD, less than 12 kD, less than 11 kD, less than 10 kD, less than 9 kD, less than 8 kD, less than 7 kD, less than 6 kD, less than 5 kD, less than 4 kD, less than 3 kD, less than 2 kD, less than 1.5 kD, less 1000 kDa, less than 900 kDa, less than 800 kDa, less than 700 kDa, less than 600 kDa, less than 500 kDa, less than 400 kDa, or less than 300 kDa.

82. The complex of claim 81, wherein the half-life extension moiety is a protein with a molecular weight of 12 kD-15 kD.

83. The complex of claim 81, wherein the half-life extension moiety is a peptide with a molecular weight of 500 Da-1 kD, 500 Da-1.5 kD, 500 Da-2 kD, 1 kD-2 kD, 1 kD-1.5 kD, or 1.5 kD-2 kD.

84. The complex of claim 81, wherein the albumin binding moiety is a protein comprising 105-140 amino acids.

85. The complex of claim 81, wherein the half-life extension moiety is a peptide consisting of 8-22, 10- 22, 10-20, 10-18, 10-16, 12-16, 12-18, 12-20, 12-22, 14-22, 14-16, 14-18, 14-20, 16-20 linked amino acids.

86. The complex of claim 81, wherein the half-life extension moiety comprises a fatty acid and has a molecular weight of less than 1000 kDa, less than 900 kDa, less than 800 kDa, less than 700 kDa, less than 600 kDa, less than 500 kDa, less than 400 kDa, or less than 300 kDa.

87. The complex of any of claims 39-63, wherein the combined molecular weight of A+T+L1+L2+L3+B is less than 50 kD, less than 45 kD, less than 40 kD, less than 35 kD, less than 30 kD, less than 25 kD, less than 20 kD, less than 15 kD, less than 10 kD, less than 5 kD, less than 4 kD, less than 3 kD, or less than 2 kD.

88. The complex of any of claims 1-87, wherein the cargo is an oligomeric agent comprising at least a first modified oligonucleotide consisting of 12-80 linked nucleosides.

89. The complex of claim 88, wherein the transferrin-receptor binding moiety is attached at the 3’-end of the first modified oligonucleotide, optionally through a first linker.

90. The complex of claim 88, wherein the transferrin-receptor binding moiety is attached at the 5’-end of the first modified oligonucleotide, optionally through a first linker.

91. The complex of any of claims 88-90, wherein the transferrin-receptor binding moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a first linker.

92. The complex of claim 91, wherein the transferrin-receptor binding moiety is attached at the 2’- position of a modified sugar moiety.

93. The complex of any of claims 88-91, wherein the half-life extension moiety is attached at the 3’-end of the first modified oligonucleotide, optionally through a second linker.

94. The complex of any of claims 88-91, wherein half-life extension moiety is attached at the 5’-end of the first modified oligonucleotide, optionally through a second linker.

95. The complex of any of claims 88-94, wherein the half-life extension moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a second linker.

96. The complex of claim 95, wherein the half-life extension moiety is attached at the 2’-position of a modified sugar moiety.

97. The complex of any of claims 88-96, wherein the half-life extension moiety is attached to the transferrin-receptor binding moiety, optionally through a linker.

98. The complex of claim 88, wherein the complex comprises a branching group, wherein the transferrin- receptor binding moiety is attached to the branching group, optionally through a first linker, the half-life extension moiety is attached to the branching group, optionally through a second linker.

99. The complex of claim 98, wherein the branching group is attached at the 3’-end of the first modified oligonucleotide, optionally through a third linker.

100. The complex of claim 98, wherein the branching group is attached at the 5’-end of the first modified oligonucleotide, optionally through a third linker.

101. The complex of any of claims 98-100, wherein the branching group is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a third linker.

102. The complex of any of claims 98-101, wherein the branching group is selected from: .any of claims 88-101, comprising at least one linker.

104. The complex of claim 102, wherein at least one linker comprises a hydrophilic moiety.

105. The complex of claim 103, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine.

106. The complex of claim 104, wherein at least one linker comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24.

107. The complex of claim 104, wherein at least one linker comprises (sarcosine)n, where is n is 1 to 10.

108. The complex of any of claims 88-97 or 103-107, wherein the transferrin receptor binding moiety and the half-life extension moiety are attached at different positions of the modified oligonucleotide.

109. The complex of claim 88, comprising a compound that is represented by one of the following formulae:  A‐L1‐T‐L2‐X  T‐L1‐A‐L2‐X  X‐L1‐T‐L2‐A  X‐L1‐A‐L2‐T  A‐L1‐X‐L2‐T  T‐L1‐X‐L2‐A  A—L1     B—L2—X         L1—A   wherein A represents an half-life extension moiety; T represents a transferrin-receptor binding moiety, X represents a modified oligonucleotide (from 5’ to 3’); each of L1, L2and L3represent an independently selected linker; and B is a branching group.

110. The complex of claim 109, wherein at least one linker comprises a hydrophilic moiety.

111. The complex of claim 110, wherein the hydrophilic moiety is an ethylene glycol or a sarcosine.

112. The complex of any of claims 109-111, wherein L1comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24.

113. The complex of any of claims 109-112, wherein L1comprises (sarcosine)n, where is n is 1 to 10.

114. The complex of any of claims 109-113, wherein L2comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24.

115. The complex of any of claims 109-114, wherein L2comprises (sarcosine)n, where is n is 1 to 10.

116. The complex of any of claims 109-115, wherein the compound comprises a branching group B, and wherein L3comprises PEG1, PEG2, PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG14, PEG16, PEG18, PEG20, PEG22, or PEG24.

117. The complex of any of claims 109-116, wherein the compound comprises a branching group B, and wherein L3comprises (sarcosine)n, where is n is 1 to 10.

118. The complex of any of claims 109-117, wherein B is a branching group selected from: .any of claims 109-118, wherein the transferrin-receptor binding moiety is selected from a peptide or protein.

120. The complex of claim 119, wherein the transferrin-receptor binding moiety is a linear peptide, a cyclic peptide, or a bicyclic peptide.

121. The complex of claim 120, wherein the transferrin-receptor binding moiety is a bicyclic peptide with a linear amino acid sequence having at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 2, 3, 21-29, or 31-191.

122. The complex of claim 119, wherein the transferrin-receptor binding moiety is a VNAR or a VHH.

123. The complex of any of claims 109-122, wherein the half-life extension moiety is an albumin- binding moiety, an FcRn-binding moiety, or an IgG-binding moiety.

124. The complex of claim 123, wherein the half-life extension moiety is an albumin-binding moiety.

125. The complex of claim 124, wherein the albumin-binding moiety is a peptide.

126. The complex of claim 125, wherein the peptide has a linear amino acid sequence with at least 80%, at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 4, 266-267.

127. The complex of claim 124, wherein the albumin-binding moiety comprises a fatty acid.

128. The complex of claim 127, wherein the albumin-binding moiety comprises a bis-lipid.

129. The complex of claim 128, wherein the bis-lipid is . moiety comprises.

132. The complex of claim 131, wherein the FcRn-binding moiety is a peptide.

133. The complex of claim 132, wherein the peptide has a linear amino acid sequence having at least 90%, at least 95%, or 100% identity to any of SEQ ID NOs: 277 or 278.

134. The complex of any of claims 88-133, wherein the oligomeric agent is single-stranded.

135. The complex of claim 134, wherein the oligomeric agent is an RNAse H agent or a splice- modulating agent.

136. The complex of any of claims 88-135, wherein the oligomeric agent comprises a second modified oligonucleotide consisting of 12-80 linked nucleosides, 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.

137. The complex of claim 136, wherein the transferrin-receptor binding moiety is attached at the 3’-end of the second modified oligonucleotide, optionally through a first linker.

138. The complex of claim 136, wherein the transferrin-receptor binding moiety is attached at the 5’-end of the second modified oligonucleotide, optionally through a first linker.

139. The complex of any of claims 136-138, wherein the transferrin-receptor binding moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the second modified oligonucleotide, optionally through a first linker.

140. The complex of any of claims 136-139, wherein half-life extension moiety is attached at the 3’-end of the second modified oligonucleotide, optionally through a second linker.

141. The complex of any of claims 136-139, wherein half-life extension moiety is attached at the 5’-end of the second modified oligonucleotide, optionally through a second linker.

142. The complex of any of claims 136-141, wherein the half-life extension moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the second modified oligonucleotide, optionally through a second linker.

143. The complex of any of claims 136 or 140-142, wherein the transferrin-receptor binding moiety is attached at the 3’-end of the first modified oligonucleotide, optionally through a first linker.

144. The complex of any of claims 136 or 140-142, wherein the transferrin-receptor binding moiety is attached at the 5’-end of the first modified oligonucleotide, optionally through a first linker.

145. The complex of any of claims 136 or 140-144, wherein the transferrin-receptor binding moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a first linker.

146. The complex of any of claims 136-139 or 143-145, wherein the half-life extension moiety is attached at the 3’-end of the first modified oligonucleotide, optionally through a second linker.

147. The complex of any of claims 136-139 or 143-145, wherein the half-life extension moiety is attached at the 5’-end of the first modified oligonucleotide, optionally through a second linker.

148. The complex of any of claims 136-139 or 143-147, wherein the half-life extension moiety is attached at a modified sugar moiety, a modified nucleobase, or a modified internucleoside linkage of the first modified oligonucleotide, optionally through a second linker.

149. The complex of any of claims 136-148, wherein the transferrin-receptor binding moiety and the half-life extension moiety are attached to the same modified oligonucleotide.

150. The complex of any of claims 136-148, wherein the transferrin-receptor binding moiety is attached to the first modified oligonucleotide and the half-life extension moiety is attached to the second modified oligonucleotide.

151. The complex of any of claims 136-148, wherein the transferrin-receptor binding moiety is attached to the second modified oligonucleotide and the half-life extension moiety is attached to the first modified oligonucleotide.

152. The complex of claim any of claims 136-149, wherein the complex comprises a branching group, wherein the transferrin-receptor binding moiety is attached to the branching group, optionally through a first linker, and wherein the half-life extension moiety is attached to the branching group, optionally through a second linker.

153. The complex of claim 152, wherein the branching group is attached at the 3’-end of the first modified oligonucleotide, optionally through a third linker.

154. The complex of claim 152, wherein the branching group is attached at the 5’-end of the first modified oligonucleotide, optionally through a third linker.

155. The complex of claim 152, wherein the branching group is attached at the 3’-end of the second modified oligonucleotide, optionally through a third linker.

156. The complex of claim 152, wherein the branching group is attached at the 5’-end of the second modified oligonucleotide, optionally through a third linker.

157. The complex of any of claims 136-156, wherein the pair of modified oligonucleotides is represented by one set of the following formulae: A‐L1‐X and T‐L2‐Y;  A‐L1‐X and Y‐L2‐T;  T‐L1‐X and A‐L2‐Y;  T‐L1‐X and Y‐L2‐T;  X‐L1‐A and T‐L2‐Y;  X‐L1‐T and A‐L2‐Y;  X‐L1‐T and Y‐L2‐A;  X‐L1‐A and Y‐L2‐T;  wherein A represents an albumin-binding moiety; T represents a transferrin-receptor binding moiety, X represents a first modified oligonucleotide (5’ to 3’), Y represents a second modified oligonucleotide (5’ to 3’); and each of L1and L2is an independently selected linker.

158. The complex of any of claims 136-157, 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.

159. The complex of any of claims 88-158, wherein the first modified oligonucleotide comprises at least one nucleoside comprising a modified sugar moiety.

160. The complex of claim 152, wherein the first modified oligonucleotide comprises at least one nucleoside comprising a non-bicyclic modified sugar moiety.

161. The complex of claim 160, wherein the non-bicyclic modified sugar moiety is a 2’-OMe sugar moiety, a 2’-MOE sugar moiety, a 2’-F sugar moiety, or a 2’-NMA sugar moiety.

162. The complex of any of claims 159, wherein the first modified oligonucleotide comprises at least one nucleoside comprising a bicyclic sugar moiety.

163. The complex of claim 162, wherein the bicyclic sugar moiety comprises a 4’-2’ bridge selected from 4'-CH2-O-2' and 4'-CH(CH3)-O-2'.

164. The complex of any of claims 136-163, wherein the second modified oligonucleotide comprises at least one nucleoside comprising a modified sugar moiety.

165. The complex of claim 164, wherein the second modified oligonucleotide comprises at least one nucleoside comprising a non-bicyclic modified sugar moiety.

166. The complex of claim 165, wherein the non-bicyclic modified sugar moiety a 2’-OMe sugar moiety, a 2’-MOE sugar moiety, a 2’-F sugar moiety, or a 2’-NMA sugar moiety.

167. The complex of claim 164, wherein the second modified oligonucleotide comprises at least one nucleoside comprising a bicyclic sugar moiety.

168. The complex of claim 167, wherein the bicyclic sugar moiety comprises a 4’-2’ bridge selected from 4'-CH2-O-2' and 4'-CH(CH3)-O-2'.

169. The complex of any of claims 88-168, wherein the first modified oligonucleotide comprises at least one modified internucleoside linkage.

170. The complex of claim 169, wherein at least one internucleoside linkage of the first modified oligonucleotide is a phosphorothioate linkage.

171. The complex of claim 169 or 170, wherein at least one internucleoside linkage of the first modified oligonucleotide is a phosphodiester linkage.

172. The complex of any of claims 169-171, wherein at least one internucleoside linkage of the first modified oligonucleotide is a mesyl phosphoramidate internucleoside linkage.

173. The complex of any of claims 88-172, wherein each internucleoside linkage of the first modified oligonucleotide is independently selected from a phosphodiester internucleoside linkage, a phosphorothioate internucleoside linkage, and a mesyl phosphoramidate internucleoside linkage.

174. The complex of any of claims 136-173, wherein the second modified oligonucleotide comprises at least one modified internucleoside linkage.

175. The complex of claim 174, wherein at least one internucleoside linkage of the second modified oligonucleotide is a phosphorothioate linkage.

176. The complex of claim 174 or 175, wherein at least one internucleoside linkage of the second modified oligonucleotide is a phosphodiester linkage.

177. The complex of any of claims 174-176, wherein at least one internucleoside linkage of the second modified oligonucleotide is a mesyl phosphoramidate internucleoside linkage.

178. The complex of any of claims 174-177, wherein each internucleoside linkage of the second modified oligonucleotide is independently selected from a phosphodiester internucleoside linkage, a phosphorothioate internucleoside linkage, and a mesyl phosphoramidate internucleoside linkage.

179. The complex of any of claims 88-178, wherein the oligomeric agent comprises nucleobases selected from uracil, thymine, cytosine, 5-methyl cytosine, adenine, guanine, and hypoxanthine.

180. The complex of any of claims 88-179, wherein the first modified oligonucleotide consists of 12 to 20, 12 to 25, 13 to 20, 13 to 25, 14 to 20, 14 to 25, 15 to 20, 15 to 25, 16 to 18, 16 to 20, 16 to 25, 17 to 20, 17 to 25, 18 to 20, 18 to 25, 19 to 20, 19 to 25, 20 to 25, 20 to 3021-23, 21 to 25, 22 to 25, 23 to 25, 23 to 30, 18, 20, 21, or 23 linked nucleosides.

181. The complex of any of claims 136-180, wherein the second modified oligonucleotide consists of 12 to 20, 12 to 25, 13 to 20, 13 to 25, 14 to 20, 14 to 25, 15 to 20, 15 to 25, 16 to 18, 16 to20, 16 to 25, 17 to 20, 17 to 25, 18 to 20, 18 to 25, 19 to 20, 19 to 25, 20 to 25, 20 to 3021-23, 21 to 25, 22 to 25, 23 to 25, 23 to 30, 18, 20, 21, or 23 linked nucleosides.

182. The complex of any of claims 136-181, wherein the oligomeric agent is an RNAi agent.

183. The complex of claim 182, wherein the oligomeric agent comprises an antisense RNAi oligonucleotide and a sense RNAi oligonucleotide.

184. The complex of any of claims 1-183, wherein the complex has a total molecular weight of less than 50 kD, less than 40 kD, less than 30 kD, less than 20 kD, or less than 10 kD.

185. The complex of any of claims 1-184, wherein the complex has a total molecular weight of 1 kD to 50 kD, 5 kD to 50 kD, 5 kD to 40 kD, 5 kD to 30 kD, 5 kD to 20 kD, 10 kD to 50 kD, 10 kD to 40 kD, 10 kD to 30 kD, 10 kD to 20 kD, or 15 kD to 25 kD.

186. A method of modulating the expression of a target nucleic acid in the CNS, comprising administering a complex of any of claims 88-185 to a subject.

187. A method of modulating the expression of a target nucleic acid in muscle, comprising administering a complex of any of claims 88-185 to a subject.

188. A method of modulating the expression of a target nucleic acid in peripheral nerve tissue, comprising administering a complex of any of claims 88-185 to a subject.

189. The method of any of claims 186-188, wherein the complex is administered systemically.

190. The method of claim 189, wherein the complex is administered intravenously.

191. The method of claim 189, wherein the complex is administered subcutaneously.

192. The complex of any of claims 1-185, for use in therapy.

193. The complex of any of claims 1-185, for use in the manufacture of a medicament.

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