Precision Biosciences, Inc.

The present disclosure encompasses nucleic acid expression constructs that regulate the expression of a heterologous protein specifically in muscle tissues (e.g., skeletal muscle and cardiac muscle tissue). In particular embodiments of the disclosure, muscle-specific expression constructs are described that encode a heterologous protein. These heterologous proteins can be any protein that is desired to be expressed in a muscle cell. In particular embodiments of the disclosure, proteins are described for the treatment of Duchenne Muscular Dystrophy (e.g., engineered nucleases such as engineered meganucleases).

The present disclosure encompasses engineered nucleases which recognize and cleave a recognition sequence within a Hepatitis B virus (HBV) genome. The engineered meganucleases described herein can exhibit improved characteristics, such as enhanced specificity and/or efficiency of indel formation, when compared to previously described HBV meganucleases. Further, the disclosure encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or diseases associated with HBV infections.

The present disclosure encompasses engineered meganucleases that comprise two subunits connected by a polypeptide linker that is smaller than polypeptide linkers used in the art. The engineered meganucleases can exhibit at least one improved characteristic, such as increased efficiency of binding and/or cleavage, when compared to meganucleases comprising longer polypeptide linkers. The present disclosure also encompasses methods of using engineered nucleases to make genetically-modified cells and the use of such cells in a pharmaceutical composition and in methods for treating diseases.

Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

The present invention encompasses engineered meganucleases that bind and cleave a recognition sequence within the first exon of the human T cell receptor (TCR) alpha constant region gene. The engineered meganucleases can exhibit at least one optimized characteristic, such as increased specificity or efficiency of cleavage, when compared to previous generations of meganucleases. The present invention also encompasses methods of using such engineered nucleases to make genetically-modified cells, and the use of such cells in a pharmaceutical composition and in methods for treating diseases, such as cancer.

The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within the int22h-1 sequence of a Factor VIII gene. The present invention also encompasses methods of using such engineered nucleases to make genetically-modified cells, and the use of such cells in a pharmaceutical composition and in methods for treating hemophilia A. Further, the invention encompasses pharmaceutical compositions comprising engineered nuclease proteins, nucleic acids encoding engineered nucleases, or genetically-modified cells of the invention, and the use of such compositions for treating of hemophilia A.

Disclosed are recombinant meganucleases engineered to bind and cleave a recognition sequence present in a mutant RHO P23H allele. The invention further relates to the use of such recombinant meganucleases in a method for treating retinitis pigmentosa, wherein the mutant RHO P23H allele is preferentially targeted, cleaved, and inactivated.

The present disclosure encompasses nucleic acid expression constructs that regulate the expression of a heterologous protein specifically in muscle tissues (e.g., skeletal muscle and cardiac muscle tissue). In particular embodiments of the disclosure, muscle-specific expression constructs are described that encode a heterologous protein. These heterologous proteins can be any protein that is desired to be expressed in a muscle cell. In particular embodiments of the disclosure, proteins are described for the treatment of Duchenne Muscular Dystrophy (e.g., engineered nucleases such as engineered meganucleases).

The present disclosure encompasses engineered nucleases which recognize and cleave a recognition sequence within a Hepatitis B virus (HBV) genome. The engineered meganucleases described herein can exhibit improved characteristics, such as enhanced specificity and/or efficiency of indel formation, when compared to previously described HBV meganucleases. Further, the disclosure encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or diseases associated with HBV infections.

The present disclosure provides antibodies, and fragments thereof, having specificity for human B cell maturation antigen, pharmaceutical compositions thereof, and uses thereof. Also provided are chimeric antigen receptors (CARs) comprising such antibodies or antibody fragments, genetically-modified cells comprising such CARs, pharmaceutical compositions comprising such cells, methods for making such cells, and methods of using such cells for the treatment of disorders and diseases, such as cancer.