Alan Stolier, MD/

CRISPR Slowly Advances into the Clinic

An article by Susan Jenks appears in a recent edition of the Journal of the National Cancer Institute (JNCI 2017;109 (10)) The articled is titled “CRISPR Slowly Advances into the Clinic.” As a review, CRISPR is an acronym standing for Clustered Regularly Interspaced Palindromic Repeats. The CRISPR technique is based on the repeated genetic code that bacteria remember and use to destroy viruses and other invaders. It was adapted for human use through genetic engineered coupling to a humanized bacterial protein, Cas9. Cas9 acts as a molecular scissors with an RNA molecule which tells it where to cut.

Current CRISPR Cas9 technology has recently passed the NIH first safety review. Small clinical trials may get underway in the U.S. by years end. However, questions remain such as uncertainties about off targeting and unintended effects during editing. For instance, editing out a gene that enables human immunodeficiency virus to infect cells, might inadvertently raise vulnerability to West Nile virus. As noted by Anthony Komoroff at Harvard, the most important question however, is how to deliver the system into every cell and into the target tissue.  He noted that delivery to each cell will be required to successfully treat cancer. He added that, “A lot of people use liquid nanoparticles, or balloons of liquids taken up by cells; whereas others use adenoviruses or lentiviruses”. It is still unclear which is better. Furthermore, Komaroff, referring to the CRISPR editing system, “it’s not perfect”. (JAMA 2017; 318:699-700)

Tyler Jacks Ph.D., director of Koch Institute noted that CRISR Cas9 has made it easy to create models of human disease. He said, “Imagine you have 25 different types of lung cancer. With this technique we can create the disease’s genetic elements in all of its complexity. That ability raises the prospect of customizing drugs to each patient with his or her own therapy…an idea no longer farfetched”. However, Ji Luo Ph.D. head of cancer systems biology at NIH noted that correcting mutations in cancer cells defies an easy fix because any cell not corrected will grow into a new tumor.

The Chinese have launched several clinical trials including one for lung cancer, and have also waded into altering genes in viable embryos. The U.S. and other western nations scientific community have agreed to pause germline interventions, which many view as an “ethical landmine”.   Recruiting for first U.S. CRISPR trial awaits FDA approval. The first trials are at the starting block appear to target T-cell modifications in various cancer patients and not germline mutations.

Despite issues with delivery and other potential pitfalls CRISPR technology is here and the good stuff, though years away is just beginning.







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