Highly targeted CRISPR delivery system advances gene editing in living animals

Enveloped viruses get their outer coat by budding from cells they’ve invaded. CRISPR-Cas9 researchers coopted this behavior to produce envelope-derived vehicles that encapsulate Cas9 proteins (dark green), guide RNA and transgenes. These loaded carriers target and invade specific types of human T-cells, where they simultaneously edit and insert new genes, turning the T-cells into cancer fighters. Credit: Jenny Hamilton, IGI/UC Berkeley

Most approved gene therapies today, including those involving CRISPR-Cas9, work their magic on cells removed from the body, after which the edited cells are returned to the patient.

This technique is ideal for targeting blood cells and is currently the method employed in newly approved CRISPR gene therapies for blood diseases like sickle cell anemia, in which edited blood cells are reinfused in patients after their bone marrow has been destroyed by chemotherapy. A new, precision-targeted delivery method for CRISPR-Cas9, published in the journal Nature Biotechnology, enables gene editing on very specific subsets of cells while still in the body a step toward a programmable delivery method that would eliminate the need to obliterate patients’ bone marrow and immune system before giving them edited blood cells.

The delivery method, developed in the University of California, Berkeley, laboratory of Jennifer Doudna, co-inventor of CRISPR-Cas9 genome editing, involves wrapping the Cas9 editing proteins and guide RNAs in a membrane bubble that has been decorated with pieces of monoclonal antibodies that home in on specific types of blood cells.

As a demonstration, Jennifer Hamilton, a CRISPR researcher in the Doudna laboratory at the Innovative Genomics Institute (IGI), targeted a cell of the immune system a T-cell which is the starting point for a revolutionary cancer treatment called chimeric antigen receptor (CAR) T-cell therapy.

By University of California – Berkeley

Article can be accessed on: phys.org