A recombinant mutant BoV genome is provided, as well as methods of using the vector, e.g., to prepare helper-free virus.

The present invention relates to innovative protoparvoviruses (PV) expressing RNAi effectors, preferably shRNAs against the PD-L1 gene which display improved anticancer activity. These new viruses are based on the ?H-1PVsilencer platform that consists of a protoparvovirus H-1PV featuring an in-frame deletion within the NS region (?H-1PV) and harbouring a shRNA expression cassette in which the expression of the shRNA is controlled by the H1 Polymerase III promoter. In this invention the inventors aimed to use the ?H-1PVsilencer to silence the PD-L1 gene. PD1/PD-L1 negatively regulates T cell-mediated immune responses and serves as a mechanism for tumors to escape antigen-specific T cell immune responses. The present invention also provides cells or organisms comprising said parvovirus.

Described are methods for efficiently down regulating the expression of a gene of interest in a cell by use of a modified rodent parvovirus that contains an expressible target specific nucleic acid, preferably an shRNA expression cassette. Also described are cells or organisms comprising said parvovirus.

The invention relates to methods of treating melanoma using a herpes simplex virus in combination with an immune checkpoint inhibitor.

A system for genetic editing of a transthyretin (TTR) gene, comprising (i) a Cas12i2 polypeptide or a first nucleic acid encoding the Cas12i2 polypeptide, and (ii) an RNA guide or a second nucleic acid encoding the RNA guide, wherein the RNA guide comprises a spacer sequence specific to a target sequence within an TTR gene. Also provided herein are methods for editing a TTR gene using the gene editing system disclosed herein and/or for treating diseases associated with the TTR gene.

Described herein are methods for treating a retinal degeneration in a subject, such as Leber's congenital amaurosis (LCA), retinitis pigmentosa (RP), and glaucoma. Also provided herein are methods of altering expression of one or more gene products in a cell, such as a retinal ganglion cell. Such methods may comprise utilizing a modified nuclease system, such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system comprising a bidirectional HI promoter and gRNAs directed to retinal degeneration related genes, packaged in a single, compact adeno-associated virus (AAV) particle.

Provided herein is a baculovirus expression vector system for the production of a desired protein. In one aspect, the desired protein is a closed-ended DNA (ceDNA) molecule comprising wild-type and/or truncated inverted terminal repeats derived from a genome of a member of the viral family Parvoviridae.

The invention relates to methods of treating melanoma using a herpes simplex virus in combination with an immune checkpoint inhibitor.

The present disclosure provides compounds comprising modified oligonucleotides for use in CRISPR. In certain embodiments, such modified oligonucleotides provide improved properties of crRNA. In certain embodiments, such modified oligonucleotides provide improved properties of scrRNA.

Provide herein are polynucleotides comprising a codon-optimized AP4M1 open reading frame (ORF) sequence encoding an AP4M1 polypeptide, vectors (viral or non-viral vectors) comprising the same, pharmaceutical compositions comprising the same, and methods of using the same for delivery of the polynucleotides to a cell or a subject and to treat AP4M1-related genetic disorders such as AP4M1 deficiency and spastic paraplegia type 50.