Abstract: Provided herein are systems comprising Class 2, Type V CRISPR proteins and guide nucleic acids (gRNA) useful in the modification of a target nucleic acid of a lipoprotein (a) (LPA) gene. The systems are also useful for introduction into cells, for example eukaryotic cells. Also provided are methods for treating subjects having a LPA-related disease and methods for optimizing the encoding sequences.

Abstract: Provided herein are gene repressor systems comprising fusion proteins, such as fusion proteins comprising a DNA binding domain such as a TALE, zinc finger or catalytically-dead CRISPR protein and guide nucleic acid (gRNA), which are useful in the repression of a proprotein convertase subtilisin/kexin Type 9 (PCSK9) gene. Also provided are methods of using such systems to repress transcription of PCSK9.

Abstract: Provided herein are engineered Class 2. Type V nucleases and guide RNAs useful for the editing of target nucleic acids. Also provided are methods of making and using such variants to modify nucleic acids.

Abstract: Provided herein are CasX:gNA systems, and compositions and methods relating thereto, the systems comprising CasX proteins, guide nucleic acids (gNAs), and optionally donor template nucleic acids useful for the modification cell genes encoding proteins involved in antigen processing, antigen presentation, antigen recognition, and/or antigen response, as well as methods of producing and using populations of cells comprising these modified genes. In some embodiments, the modified cells further express chimeric antigen receptors (CAR) or engineered T cell receptors (TCR). Such systems are useful for preparing cells for immunotherapy.

Abstract: The disclosure relates to gene repressor systems comprising catalytically-dead Class 2 CRISPR proteins and one or more transcription repressor domains linked to the catalytically-dead Class 2 CRISPR protein as a fusion protein, as well as a guide ribonucleic acid (gRNA); and methods of making and using same.

Abstract: Provided herein are gene repressor systems comprising fusion proteins, such as fusion proteins comprising a DNA binding domain such as a TALE, zinc finger or catalytically-dead CRISPR protein and guide nucleic acid (gRNA), which are useful in the repression of a proprotein convertase subtilisin/kexin Type 9 (PCSK9) gene. Also provided are methods of using such systems to repress transcription of PCSK9.

Abstract: Provided herein are recombinant adeno-associated virus (rAAV) compositions and methods for use of the rAAV encoding CasX proteins and guide ribonucleic acid (gRNA) sequences useful for nucleic acid sequence editing, and including transgene components. The rAAV may be delivered to cells to target a gene of interest.

Abstract: Provided herein are systems of engineered Class 2, Type V nucleases and guide ribonucleic acid scaffolds useful for the editing of target nucleic acids. Also provided are methods of making and using such systems to modify nucleic acids.

Abstract: Provided herein are catalytically dead engineered proteins, e.g., catalytically dead CasX proteins. Also provided herein are systems comprising guide nucleic acids and catalytically dead engineered proteins, and methods for use thereof.

Abstract: Provided herein are gene editing pairs comprising an engineered protein, e.g, an engineered CRISPR protein and a guide ribonucleic acid (gRNA) that may provide improved gene editing relative to reference, i.e., wild type sequences. In some embodiments, the engineered protein of the gene editing pair comprises a RuvC cleavage domain with one or more amino acid modifications relative to a reference CRISPR protein RuvC sequence. In some embodiments, a guide ribonucleic acid (gRNA) of the gene editing pair comprises at least one modification in a scaffold stem loop relative to a reference scaffold stem loop sequence.

Abstract: Provided herein are engineered Class 2, Type V nucleases and guide RNAs useful for the editing of target nucleic acids. Also provided are methods of making and using such variants to modify nucleic acids.

Abstract: Provided herein are engineered Class 2, Type V nucleases and guide RNAs useful for the editing of target nucleic acids. Also provided are methods of making and using such variants to modify nucleic acids.

Abstract: The disclosure relates to gene repressor systems comprising catalytically-dead Class 2 CRISPR proteins and one or more transcription repressor domains linked to the catalytically-dead Class 2 CRISPR protein as a fusion protein, as well as a guide ribonucleic acid (gRNA); and methods of making and using same.

Abstract: Provided herein are engineered Class 2, Type V nucleases and guide RNAs useful for the editing of target nucleic acids. Also provided are methods of making and using such variants to modify nucleic acids.

Abstract: Provided herein are compositions and methods for use of self-inactivating recombinant vectors (SIRV) encoding Class 2 Type V and guide ribonucleic acid (gRNA) sequences useful for nucleic acid sequence editing, and including self-inactivating components. The SIRV may be delivered to cells as part of an AAV vector to target a gene of interest.

Abstract: Provided herein are Class 2 Type V systems comprising nucleases, guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a C9orf72 gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations or duplications in the C9orf72 gene. Also provided are methods of using such systems to modify cells having such mutations or duplications.

Abstract: Provided herein are reference guide nucleic acid scaffolds and variants of reference guide nucleic acid scaffolds capable of binding one or more engineered proteins comprising a RuvC cleavage domain. In some embodiments, the variants of the reference guide nucleic acid scaffolds comprise at least one modification compared to the reference guide nucleic acid scaffold sequences and exhibit one or more improved characteristics compared to the reference guide nucleic acid scaffolds.

Abstract: The disclosure relates to gene repressor systems comprising catalytically-dead Class 2 CRISPR proteins and one or more transcription repressor domains linked to the catalytically-dead Class 2 CRISPR protein as a fusion protein, as well as a guide ribonucleic acid (gRNA); and methods of making and using same.

Abstract: Provided herein are glycoprotein particles comprising one or more glycoproteins, or fragments thereof that enhance targeting of a particle to a cell or tissue. A glycoprotein particle as provided herein may be used for any application, including therapeutic and diagnostic treatments.

Abstract: Provided herein are delivery particle systems (XDP) useful for the delivery of payloads of any type. In some embodiments, a XDP particle system with tropism for target cells of interest is used to deliver CRISPR/Cas polypeptides (e.g., CasX proteins) and guide nucleic acids (gNA), for the modification of nucleic acids in target cells. Also provided are methods of making and using such XDP to modify the nucleic acids in such cells.