The invention relates to methods of reducing the immunogenicity of CRISPR-associated (Cas) proteins and the modified Cas proteins produced therefrom. In addition, the invention relates to methods for cell and gene therapy, including any and all genetic modifications and alterations of gene expression (and/or genetic elements) made in-vivo or ex-vivo using Cas proteins with reduced immunogenicity.

The invention relates to biotechnology. The claimed agent can be used for the prevention of SARS-CoV-2.

A pharmaceutical agent may contain component (1), and contains a recombinant human adenovirus serotype genome (26), with an expression cassette selected from SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, and also contains component (2), comprising an agent selected from (i) a recombinant human adenovirus serotype genome (5), with an expression cassette selected from SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3; or (ii) a recombinant simian adenovirus serotype genome (25), with an expression cassette selected from SEQ ID NO: 4, SEQ ID NO: 2, or SEQ ID NO: 3.

Furthermore, a pharmaceutical agent may contain component (1), comprising an agent comprising a recombinant simian adenovirus serotype genome (25), with an expression cassette selected from SEQ ID NO: 4, SEQ ID NO: 2, or SEQ ID NO: 3, and also contains component (2), comprising an agent comprising a recombinant human adenovirus serotype genome (5), with an expression cassette selected from SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.

Provided herein are AAV8 mutant capsids and rAAV comprising the same. In one embodiment, vectors employing the AAV8 mutant capsid show increased transduction in a selected tissue as compared to AAV8.

During lung fibrosis, activation of fibroblasts to myofibroblasts, is accompanied by the increased assembly of extracellular matrix proteins fibronectin and collagen. Activated myofibroblasts are key drivers of fibrosis; and increased deposition of the assembled matrix proteins, preserves the myofibroblast state. These changes contribute to enhanced tissue stiffness, collagenous deposition known as fibroblastic foci in lung and therefore, established pulmonary fibrosis. The present invention identifies a novel function of the 40 amino acid SOCS domain peptide (SEQ ID NO:1), in degrading the pathologic fibronectin and collagen matrix associated with fibrosis, markedly reducing the myofibroblast protein α-SMA and reducing collagen deposits in the fibrotic lung, leading to fibrosis reversal. Use of the SOCS domain peptide is a new approach to treat lung fibrosis as it restricts extracellular matrix assembly and reverses myofibroblasts to fibroblasts.

Provided herein are AAV8 mutant capsids and rAAV comprising the same. In one embodiment, vectors employing the AAV8 mutant capsid show increased transduction in a selected tissue as compared to AAV8.

Provided herein are compositions and methods for the viral gene therapy (e.g., AAV-directed gene therapy) of cholesterol storage diseases or disorders, such as Niemann-Pick disease, Type C

A combination of cationic nanoparticles and viruses and uses thereof. The use of nanoparticles for enhancing the infectious capacity of a live virus, preferably a non-enveloped live virus.

Provided herein are AAV8 mutant capsids and rAAV comprising the same. In one embodiment, vectors employing the AAV8 mutant capsid show increased transduction in a selected tissue as compared to AAV8.

The invention relates to methods of reducing the immunogenicity of CRISPR-associated (Cas) proteins and the modified Cas proteins produced therefrom. In addition, the invention relates to methods for cell and gene therapy, including any and all genetic modifications and alterations of gene expression (and/or genetic elements) made in-vivo or ex-vivo using Cas proteins with reduced immunogenicity.

The present invention relates to variant AAV capsid polypeptides containing designed ankyrin repeat proteins (DARPins), wherein the variant capsid polypeptides exhibit an enhanced neutralization profile, increased transduction, and/or tropism in human liver and/or hepatocyte cells, or human pancreas and/or pancreatic cells, as compared to capsid polypeptides that do not include DARPins.