Research & Development

A new system has been developed at UCSF which uses CRISPR-Cas9 gene editing to re-engineer large quantities of cells for therapeutic applications.

A paper published in Nature Biotechnology both describes and shows how the new technology can be used to create CAR T cells, which could potentially help treat multiple myeloma ‒ ablood cancer ‒ as well as rewrite gene sequences predisposed to rare and inherited immune disorders.

The approach inserts notably long DNA sequences efficiently to precise areas of a genome cell, without using the typical viral delivery system.

CRISPR-Cas9 has historically been used as a basic research tool. It edits genes inside living cells, turning them off, deleting them, replacing them if a gene is mutated, or boosting cancer-fighting activity. In order to do this, viral vectors ‒ the inactive shells of viruses ‒ are used to carry the DNA into the gene.

Clinical trials have started where CRISPR-Cas9 has been used to generate living cell therapies. However, progress has been thwarted due to safety concerns surrounding the manufacture of bulk amounts of clinical-grade viral vectors, as well as the inability of the researchers to completely control the insertion of the viral vector.

The recent study modified CRISPR-Cas9 so that viral vectors weren’t needed by using both singlestranded and double-stranded DNA.

“One of our goals for many years has been to put lengthy DNA instructions into a targeted site in the genome in a way that doesn’t depend on viral vectors. This is a huge step toward the next generation of safe and effective cell therapies,” stated Alex Marson, MD, PhD, Director of the Gladstone-UCSF Institute of Genomic Immunology, and senior author of the study.