Development of Safe and Effective Methods of Biomolecule Delivery
Adeno-associated virus (AAV) is commonly used to administer genome editing agents, like CRISPR, to cells and tissues. Traditional AAV vectors induce long-lived expression of genome editing agents which may lead to detrimental side-effects like off-target editing (left). The Miller lab is engineering novel AAV vectors to reduce their expression time which, in turn, reduces the potential of toxic off-target editing (right).
Scripps Research Fellow Shannon Miller is using protein engineering and directed evolution to develop safer and more effective methods for the therapeutic delivery of biomolecules. This opens potential avenues for the clinical progression of gene therapies such as genome editing.
Genome editing shows promise as a one-time curative therapy for genetic disorders. However, with permanent cures arise the potential of permanent side effects. Scripps Fellow Shannon Miller and her team at Scripps Research are using modern methods of biological engineering to develop novel versions of a popular delivery vehicle, the adeno-associated virus, for improved genome-editing use with reduced potential off-target editing. To do this, they are changing the component packaged within the virus to reduce the window of time in which the genome-editing agent is in contact with the genome; more transient activity can still function effectively at the target site without the chance of performing edits at off-target sites leading to detrimental side-effects including cancer and cell death. The Bachrach Family Foundation’s support is instrumental in establishing the feasibility of this technology and demonstrating its potential for future use in genome-editing therapies.
