Gene Therapy is the Path to a Cure

Keith R. Jerome, MD, PhD

Fred Hutchinson Cancer Research Center

Seattle, Washington USA

Timothy Brown

Why gene therapy?

HIV is a genetic disease

Cure is a matter of specificity

The specificity problem

Any approach targeting epigenetic modification will have significant effects on cellular gene regulation

What is needed is the ability to specifically target and modify critical gene sequences

DNA

ATCGGAGCATCCGAT

Targeted DNA editing enzymesprovide the needed specificity

Specifically recognize and alter desired DNA sequences, while leaving other sequences intact

Homing endonucleases recognition site: 22 bp

422 > 17x1012 >>> 3x109

Approaches to HIV Gene Therapy

CCR5 modification

T cells, stem cells

Other modifications of hematopoietic cells

entry inhibitors, siRNA

Direct targeting of integrated virus

Tilton and Doms, 2010

Research agenda to bring this to reality

Further development and testing of specifically targeted, non-toxic DNA modifying enzymes

Identification of the highest yield cellular targets for modification

Techniques for modification and reintroduction of stem cells, without the need for toxic conditioning regimens

Development of highly efficient delivery vectors

Why gene therapy?

Principle has been proven in the only HIV cure to date

New breakthroughs in DNA targeting enzymes and stem cell biology mean that all the needed tools are now in hand

Gene Therapy is the Path to a Cure