The present invention generally relates to composition matters and methods useful for gene delivery and an option for therapeutic treatment of various diseases. Particularly, this disclosure relates to a plasmid vector comprising a fusion of a plurality of genes comprising a gene of a chemokine or a cytokine, a gene for a targeting polypeptide and genes for one or more polypeptide linkers. Methods of use and composition matters are within the scope of this disclosure.

The invention described herein provides compositions and reagents for assembling a tripartite complex at a specific location of a target DNA. The invention also provides methods for using the complex to, for example, label a specific genomic locus, to regulate the expression of a target gene, or to create a gene regulatory network.

It was now found that the expression of a nucleotide sequence as described in the method of the invention in a plant cell results in much higher rates of indels compared to those seen in cells transformed with a control nucleic acid molecule. Thus, the invention is directed to codon-optimized Cas9 endonuclease-encoding polynucleotide. Accordingly, the present invention provides a method for modifying a target site in the genome of a plant cell, the method comprising providing one or more guide RNA and a Cas endonuclease to said plant cell, wherein said guide RNA and Cas endonuclease are capable of forming a complex that enables the Cas endonuclease to introduce a double strand break at said target site, and wherein the Cas9 endonuclease is expressed in the plant cell from a polynucleotide comprising an codon-optimized Cas9 endonuclease encoding nucleic acid molecule with a nucleotide sequence selected from the disclosed nucleotide sequences.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes a survival factor, wherein the genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor.

Provided herein are, inter alia, compositions and methods for manipulation of genomes of living organisms.

The present disclosure is directed to compositions and methods for the treatment of Metabolic Liver Disorders. The compositions and methods can comprise an adeno-associated virus (AAV) piggyBac polynucleotide comprising a transgene. The transgene may comprise ornithine transcarbamylase (OTC) or methylmalonyl-CoA mutase (MUT1).

Provided are compositions, methods, and kits for CRISPR-based editing of DNA targets by Type I CRISPR-associated (Cas) enzymes.

Provided are compositions and methods for activating latent Human Immunodeficiency Virus (HIV). The compositions and methods may utilize a recombinant peptide that has a DNA binding zinc finger domain specific to the HIV long terminal repeat (LTR) sequence. The recombinant peptide may also have a transcription factor (e.g. a transcription activator) that is conjugated to the zinc finger domain. Also provided are methods of treating HIV in a subject in need of the treatment. The method may involve activation of latent HIV in cells of the subject and selectively removing such cells from the subject, providing complete and effective treatment of HIV.

Methods and composition for modulating a target genome and stable integration of a transgene of interest into the genome of a cell are disclosed.

The present disclosure provides expression vectors and bacterial sequence-free vectors, such as ministring DNA (msDNA), for producing virus-like particles (VLPs) as well as compositions and methods thereof. In some aspects, the methods include treating viral infections in subjects with the vectors, compositions, and VLPs.