Brief description not available

Brief description not available

Brief description not available

Scientists have developed a CRISPR-Cas9 based genome editing method for universal correction of disease-causing mutations in the CTLA4 gene, which most commonly manifest as a Primary Immunodeficiency. Current treatment involves monthly IV injections or weekly subcutaneous injections of a recombinant CTLA4-Ig fusion protein abatacept. This invention includes one-time infusion of a CTLA4-corrected autologous T cell therapy. The corrected patient cells are generated by ex vivo electroporation of a specific gRNA:Cas9 ribonucleoprotien (RNP) complex and cognate homology-directed-repair template (HDRT) targeting a functional copy of the CTLA4 gene within an intronic region of the endogenous CTLA4 gene. This combination allows for (1) highly efficient knockin (up to 70% in patient cells), (2) cell-type and context specific regulation of CTLA4 expression under natural promoter and regulatory elements, and (3) preservation of endogenous CTLA4 expression in uncorrected cells.

Brief description not available

This technology presents a way to treat human genetic disease caused by haploinsufficiency and reduced protein production. The method employs the use of adeno-associated viral (AAV) vectors for the in vivo delivery of a CRISPR-based gene expression activator (CRISPRa) that boosts transcription from the existing functional copy of the affected gene.

This invention identifies a novel class of natural protein-based inhibitors of CRISPR-Cas9, which could eliminate off-target effects of Cas9-mediated gene editing. It also presents an attractive antibiotic strategy and a potential biodefense agent against CRISPR bioterror threat.

This invention establishes a new approach to treating liver fibrosis using gene therapy.

This invention enables highly effective experimental and therapeutic genomic engineering of primary human T cells and other hematopoietic cells with CRISPR/Cas9 ribonucleoprotein (RNP) technology.  

This invention is a novel method using optimized small guide RNAs (sgRNAs) to enable dynamic imaging, editing and regulation of specific genomic elements in living mammalian cells via the CRISPR system.

The use of cell transplantation in the brain shows great promise for the treatment of human neurological diseases, such as Parkinson's disease or stroke. Indeed, pre-clinical studies in animal models have shown significantly improved neurological function following cell grafting. However, in human trials the results have been considerably more variable. This has, in part, been attributed to concerns with poor cell distribution within the target area. A further issue that has arisen with the challenge of scaling up from animal models to humans is the increase in the number of transcortical penetrations required to deliver therapeutic agents. For surgical cell transplantation approaches, cell sedimentation and impaired graft viability are also concerns that need to be addressed to optimize the use of this therapeutic avenue.

Small duplex RNAs have been shown to activate the expression of therapeutically relevant genes in a sequence-specific manner. UCSF researchers have identified chemical modifications and sequence features that enhance the activity and specificity of such duplex RNAs on targeted gene activation.