Nucleic acid constructs and compositions that allow insertion and/or expression of a retinoschisin coding sequence are provided. Nuclease agents targeting RS1 loci are provided. Compositions and methods of using such constructs for integration into a target genomic locus and/or expression in a cell are also provided. Methods of treating X-linked juvenile retinoschisis using the nucleic acid constructs and compositions are also provided.

Compositions and methods for targeting pre-determined DNA sequences in bacterial cells are provided. The methods result in the targeted elimination of bacterial cells that comprise the pre-determined DNA sequence(s). Compositions comprise DNA constructs comprising nucleotide sequences that encode a Cms1 protein operably linked to a promoter that is operable in the cells of interest. Methods to use these DNA constructs to selectively target and eliminate bacterial cells that harbor the targeted DNA sequence(s) are described herein.

The present disclosure relates to base-editing systems including a fusion protein including a DNA-binding domain and a cytidine deaminase domain and a non-protein uracil-DNA glycosylase inhibitor, and methods of using the same. The DNA-binding domains of base-editing systems of the present disclosure include domains with a variety of target region possibilities, which increase the number and type of sequences that can be edited. The npUGIs of the base-editing systems of the present disclosure improve UDG inhibition (e.g., UDG inhibition is more complete) and are suitable for use in a wide range of organisms.

Compositions, systems and methods for delivering CRISPR/Cas9-based genome editing system and a donor protein to a cell.

The present invention belongs to the field of genetic engineering. Specifically, the present invention relates to a gene editing system derived from Flavobacterium and uses thereof.

Provided herein are nucleic acids useful as guide nucleic acids (gNAs), e.g., guide ribonucleic acids (gRNAs), in a CRISPR system wherein the guide nucleic acids contain one or more modifications to one or more nucleotides, use of such guide nucleic acids in modifying cells, and other uses wherein CRISPR Cas proteins are utilized.

Embodiments of the disclosure encompass systems, methods, and compositions related to selective advantages to somatic cells that harbor one or more particular genetic modifications. In particular embodiments, there is selective expansion of gene-targeted cells wherein the strategy involves deletion of an essential gene product that is replaced with targeted integration that also includes integration of a therapeutic transgene. The cells that harbor the replaced essential gene product, and thereby the therapeutic transgene, are selected for using pharmaceutical or nutritional agents that are linked to the function of the essential gene product.

The present disclosure provides compositions and methods for treating joint disorders that are characterized by an inflammatory component. In some aspects, the compositions and methods are to prevent the progression of osteoarthritis and other arthritides and to treat osteoarthritis and other arthritides in a mammalian joint.

The present disclosure describes compositions of matter comprising a ribonucleoprotein complex comprising a nucleic acid-guided nuclease and a guide RNA, and further comprising and a blocking nucleic acid molecule represented by Formula I, wherein Formula I in the 5′-to-3′ direction comprises: A-(B-L).sub.J-C-M-T-D; wherein A is 0-15 nucleotides in length; B is 4-12 nucleotides in length; L is 3-25 nucleotides in length; J is an integer between 1 and 10; C is 4-15 nucleotides in length; M is 1-25 nucleotides in length or is absent, wherein if M is absent then A-(B-L).sub.J-C and T-D are separate nucleic acid strands; T is 17-135 nucleotides in length and comprises at least 50% sequence complementarity to B and C; D is 0-10 nucleotides in length and comprises at least 50% sequence complementarity to A; and wherein the blocking nucleic acid molecule comprises a sequence complementary to a gRNA.

The current invention provides methods of combinatorial genetic screening in a cancer cell comprising an enhanced CRISPR-Cas12a system, and compositions comprising the same. Also provided are methods for screening for synergistic combinations of drug targets, as well as the treatment of cancer in a subject in need thereof.