Complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide are provided. Compositions and methods for delivery of complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide to mammals for both research and therapeutic use are provided. Methods of treating or reducing one or more symptoms of type 2 diabetes, prediabetes and/or gestational diabetes are provided.

Provided is a bispecific recombinant protein, comprising a high affinity tumor-targeting arm and a low affinity fusion protein blocking the interaction of CD47 with SIRPα. The antibody corresponding to the high affinity tumor-targeting arm does not bind to CD47, and its binding affinity to the target antigen on the tumor cell is at least 6 times as great as the binding affinity of monomer fusion protein homodimer corresponding to the low affinity fusion protein blocking the interaction of CD47 with SIRPα, to a CD47 on the tumor cell, wherein the low affinity fusion protein blocking the interaction of CD47 with SIRPα comprises a SIRPα extracellular truncation. Also provided are nucleic acid molecules encoding recombinant proteins and the use of the recombinant proteins and nucleic acid molecules in the manufacture of a medicament for treating tumors.

Provided are chimeric cytokine modified antibodies containing an ultralong CDR3, such as based on a bovine antibody sequence or a humanized sequence thereof, in which a portion of the CDR3 of the heavy chain is replaced by an interleukin (IL-15) or IL-2, and related antibodies. Among provided antibodies are chimeric IL-15 cytokine modified antibody molecules that are further linked or complexed with an extracellular portion of the IL15Rα, such as the IL15Rα sushi domain. Also provided are methods of making and using the chimeric cytokine modified antibodies.

Provided are chimeric cytokine modified antibodies containing an ultralong CDR3, such as based on a bovine antibody sequence or a humanized sequence thereof, in which a portion of the CDR3 of the heavy chain is replaced by an interleukin (IL-15) or IL-2, and related antibodies. Among provided antibodies are chimeric IL-15 cytokine modified antibody molecules that are further linked or complexed with an extracellular portion of the IL15Rα, such as the IL15Rα sushi domain. Also provided are methods of making and using the chimeric cytokine modified antibodies.

Provided herein are 2′-O-methyl 3′phosphorothioate (MS)-modified synthetic nucleic acid molecules (single guide RNAs (sgRNAs)) in combination with a base editor as a ribonucleoprotein (RNP) complex for an electroporation-based ex vivo targeted gene disruption of the BCL11A erythroid enhancer's +55, +58, or +62, functional regions. Also provided herein are methods relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels.

The present disclosure provides for antibody-oligonucleotide conjugates, methods of preparation thereof, and methods of use thereof. Also provided are related compounds, compositions and kits.

The present disclosure provides for antibody-oligonucleotide conjugates, methods of preparation thereof, and methods of use thereof. Also provided are related compounds, compositions and kits.

Peptides and Peptide-lipid conjugates are provided in which the peptide has the general Formula (I)

##STR00001## wherein, A.sup.1 is selected from serine, threonine, O—C.sub.1-6 alkyl serine, and O—C.sub.1-6 alkyl threonine; A.sup.2 is selected from serine, threonine, O—C.sub.1-6 alkyl serine, and O—C.sub.1-6 alkyl threonine; A.sup.3 is selected from glutamic acid, glutamine, asparagine, and aspartic acid; A.sup.4 is proline; each A.sup.5 is independently selected from a natural or modified amino acid;
The peptide-lipid conjugates can be used in lipid formulations for the delivery of nucleic acids.

Peptides and Peptide-lipid conjugates are provided in which the peptide has the general Formula (I)

##STR00001## wherein, A.sup.1 is selected from serine, threonine, O—C.sub.1-6 alkyl serine, and O—C.sub.1-6 alkyl threonine; A.sup.2 is selected from serine, threonine, O—C.sub.1-6 alkyl serine, and O—C.sub.1-6 alkyl threonine; A.sup.3 is selected from glutamic acid, glutamine, asparagine, and aspartic acid; A.sup.4 is proline; each A.sup.5 is independently selected from a natural or modified amino acid;
The peptide-lipid conjugates can be used in lipid formulations for the delivery of nucleic acids.

Provided herein are methods and compositions for treating a subject suffering from a deficiency in α-L-Iduronidase in the CNS. The methods include systemic administration of a bifunctional fusion antibody comprising an antibody to a human insulin receptor and an α-L-Iduronidase. A therapeutically effective systemic dose is based on the specific CNS uptake characteristics of human insulin receptor antibody-α-L-Iduronidase fusion antibodies as described herein.