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.

Disclosed is a method for production of a fusion protein in which an antibody and a lysosomal enzyme are fused. The method comprises; (a) a step of culturing mammalian cells producing the fusion protein in a serum-free medium to let the mammalian cells secrete the fusion protein in the culture medium, (b) a step of collecting culture supernatant by removing the mammalian cells from the culture medium, and (c) a step of purifying the fusion protein from the culture supernatant by using a column chromatography employing as a solid phase a material to which a substance having affinity for the fusion protein has been bound, a column chromatography employing as a solid phase a material having affinity for the phosphate group, and a size exclusion column chromatography.

Disclosed is a method for production of a fusion protein in which an antibody and a lysosomal enzyme are fused. The method comprises; (a) a step of culturing mammalian cells producing the fusion protein in a serum-free medium to let the mammalian cells secrete the fusion protein in the culture medium, (b) a step of collecting culture supernatant by removing the mammalian cells from the culture medium, and (c) a step of purifying the fusion protein from the culture supernatant by using a column chromatography employing as a solid phase a material to which a substance having affinity for the fusion protein has been bound, a column chromatography employing as a solid phase a material having affinity for the phosphate group, and a size exclusion column chromatography.

Provided herein are dimeric IL-7-Fc fusion proteins that include Fc domains and one or more IL-7s. Also provided herein are variant IL-7s with modifications to reduce heterogeneity and/or reduced affinity/potency. Such variant IL-7s are useful, for example, in the subject dimeric IL-7-Fc fusion proteins. The dimeric IL-7-Fc fusion proteins can be used for applications where increased IL-7 activity is useful, for example, for increasing the proliferation of lymphocyte populations in mounting an anti-tumor response in a subject in need thereof.

Disclosed herein are methods and compositions for inactivating TCR and/or HLA genes, using engineered nucleases comprising at least one DNA binding domain and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided.

In certain aspects, the disclosure provides multispecific binders (e.g., ActRIIA:TβRII heteromultimers comprising an ActRIIA polypeptide and a TfiRU polypeptide). The disclosure further provides that such multispecific binders (e.g., ActRIIA:TβRII heteromultimer) may be used to treat various disorders or conditions.

Aspects of the invention include a method for synthesizing a peptide brush polymer, the method comprising: exposing a mixture comprising peptide-containing monomers, one or more photoinitiators, and one or more chain transfer agents to a light sufficient to induce photopolymerization, and photopolymerizing the peptide-containing monomers in the mixture; wherein: the resulting peptide brush polymer comprises at least one peptide-containing polymer block; the at least one peptide-containing polymer block is characterized by a degree of polymerization of at least 10 and a peptide graft density of 50% to 100%; and at least one peptide moiety of the at least one peptide-containing polymer block has 5 or more amino acid groups.

The present invention provides a fusion polypeptide comprising a target polypeptide moiety and a self-aggregating peptide moiety, and a method of producing and purifying a target polypeptide by expressing the fusion polypeptide.

A lipid composition containing a nucleic acid, wherein the lipid composition comprises a peptide-lipid conjugate, is provided. The peptide of the peptide-lipid conjugates can be from 4 to 52 amino acids in length. Methods of using the lipid composition in the in vivo delivery of nucleic acids are further provided.

A lipid composition containing a nucleic acid, wherein the lipid composition comprises a peptide-lipid conjugate, is provided. The peptide of the peptide-lipid conjugates can be from 4 to 52 amino acids in length. Methods of using the lipid composition in the in vivo delivery of nucleic acids are further provided.