HIV resistance, comparing ways to edit genes and longevity

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Gene editing to create resistance to HIV. A widely written about study in this week’s New England Journal of Medicine brought smiles to many faces at CIRM this week, because the study suggests one of our projects has a real chance of letting people living with HIV neuter the infection. The New York Times did a nice job of describing the nuances of the study from a team at the University of Pennsylvania. The Times’ Denise Grady describes this first in-human use of gene editing to disable a gene. In this case the gene knocked out of service is the one that makes the protein that HIV uses to enter a cell. Without it, the virus cannot infect the immune system’s T cells that it is so notorious for destroying. This was only a phase 1 study designed to test the safety of the method, and it did show the treatment was safe, but it also showed that many of the altered T-cells seemed resistant to the virus.

The gene editing technology used in this study is the same one being used by the CIRM-funded Disease Team at City of Hope that hopes to develop a functional cure for HIV. Both groups are using the zinc finger gene editing method developed at Sangamo Biosciences. In the Penn study, the team made the gene alteration in adult T-cells that have a limited life span in our bodies. Half of the transplanted T cells in the Penn patients were gone after one year. Our team plans to make the same gene edits in the blood forming stem cells of patients. Because those cells can multiply forever and produce all the cells of the immune system, they should be able to provide a life-time supply of T cells that are resistant to HIV infection.

Comparing ways to edit our genes. Gene therapy for the past two decades has been about inserting genes, usually carried by a virus, so that patients produce a normal protein to correct a genetic error they were born with. But over the past couple of years a whole new, much more subtle approach, has developed. Researchers are now editing the genes people were born with rather than inserting new genes. That is the focus of our HIV project I wrote about above. But the zinc finger technology used in that work is just one way of doing gene editing. A few other methods are coming into broad use. One called TALEN and one called CRISPR, are compared along with zinc fingers in a nice analysis by Genetic Engineering and Biotechnology News.

CIRM has seven gene therapy projects moving toward the clinic using a mix of traditional gene insertion and gene editing technologies. Always preferring to take more than one shot on goal we fund a second team trying to use gene editing to create T cells immune to HIV. That team is using a fourth technique not mentioned by Gen News. It using a form of the genetic intermediary, RNA, to silence the protein HIV uses to enter cells and is already in clinical trials modifying the stem cells of patients with HIV.

Longevity institute to use genetics and stem cells. Craig Venter announced the launch of a new company in the San Diego area this week that hopes to tackle human longevity by marrying to technologies, genetic mapping and stem cell therapy. The company plans to sequence 40,000 human genomes a year to start and scale up to 100,000 per year. They will be looking at a wide variety of people, including centenarians, to try to better understand the causes of diseases of aging. They then hope to use that knowledge to direct potential stem cell therapies. It is a hugely ambitious proposal, but coming from the man who took on the federally financed project to sequence the human genome for the first time, it should be taken seriously. Many would call the result of that first race a draw, so I would say this is a start-up company worth watching. Reuters picked up the press release from the fledgling company.

Student paper does nice take on stem cell work. Having cut my writing teeth at student papers, first in high school and then in college, I like giving a shout out to a student paper that does a nice job. The Daily Californian from the University of California at Berkeley did a review of the work of CIRM grantee David Schaffer that is focused on growing new dopaminergic neurons for Parkinson’s disease. The student author explains some of the science behind it, the need to use CIRM’s protected state funding to move forward with the embryonic stem cell work and some of the controversy in the field. Also, being 2014, unlike in my days as a student journalist, she included a video to make a multimedia package.

Don Gibbons