OPINION
DOCTORS Lounge
In other words , we could now target , and edit , a single gene .
That is not gene therapy as previously understood : that involved adding genes to certain cells . Gene editing involves changing specific genes inside the cells . Pre-CRISPR , a 2009 stem cell trial targeting the CCR5 gene , which is critical for HIV replication , was done in a man with both HIV and AML . But that was very labor-intensive gene editing . The CRISPR-CAS9 technique is even now being promoted in sales of less than $ 200 “ do it yourself ” gene lab kits .
What do we do with that information ? What should we do with that information ?
In China , there are already about 20 clinical trials in the works or underway . The first clinical reports of a very small Phase-1 trial came in October 2016 , when doctors led by Lu-You at the Sichuan University inserted CRISPR-modified cells into a patient with metastatic non-small cell lung cancer . The immune cells had been edited outside the body to disable the production of PD-1 , which slows the immune response to cancer ( when that protein is disabled , the immune system fights off the cancer cells more effectively ). The edited cells were cultured and then injected back into the patient .
In the US , an NIH Advisory Committee on June 21 approved Dr . Edward Stadtmauer ’ s Phase-1 trial ( funded by former Facebook exec Sean Parker ’ s $ 250 million immunotherapy foundation ). The trialists plan to remove T cells from 18 people with various cancers and use three separate gene edits , then infuse them back . One edit detects and targets the cancer cells ; the second removes a T cell protein that would block the targeting process ; the third prevents the cancer cells from identifying and disabling the immune cells that fight them off . The research team will now have to pass its own institutional review boards .
Other means of gene editing include the TALENS method and the zinc-finger nuclease ( my fave scientific name in ages ). Both are being pursued now as well . Sangamo Technologies , a biotech company , is recruiting patients for an inside-the human-body gene editing study for patients with Hemophilia B , Hurler Syndrome ( lysosomal storage disease with average lifespan under 10 years ) and Hunter Syndrome ( another storage disease whose severe form is usually lethal by age 15 ). A new , functional gene will be inserted into the gene for albumin , a protein in liver cells , said to be a “ safe harbor ” for this type of therapy . The zinc-finger nuclease method involves “ tinier ” ( if one can imagine smallness on that scale ) delivery systems into the targeted cell , and requires only one “ anchor ” to attach , both considered advantages over the CRISPR method .
The risk of CRISPR is cited as when the delivered “ missile ” makes only a partial match , but enough to latch on to its target , and therefore target the wrong process . Previous immune-therapy agents have had multiple dangerous side effects , but none has used this particular method . It ’ s stepping into the unknown , which is a familiar feeling for cancer patients and doctors .
Patients with Sickle Cell and Huntington ’ s Chorea could have their lives changed forever , if these single-gene diseases could be targeted and eliminated inside them . Women with the BRCA gene have already contacted gene researchers and asked to be notified of actual trials .
The “ eugenic ” scenario of germline editing – changing the reproductive cells – has been a hot topic in scientific circles since the invention of CRISPR . Are we going to make designer children , or designer warriors , or designer football players ? Are we going to target non-lethal but life-changing genetic disorders like Down Syndrome ? Germline editing affects not only the patients involved , but their descendants , and their descendants , so on . Because of this , the National Academy of Sciences and the National Academy of Medicine in February released a joint position statement recommending a ban on germline research in the USA . Much more study will have to be done , they said , and many ethical concerns raised and discussed , and scientific and moral consensus must first be reached .
In contrast , gene-editing therapy for somatic cells was felt to offer great promise , at currently unknown risk , and they recommended proceeding with utmost caution and all due process . Gene editing holds out the promise of curing heretofore incurable inherited diseases .
That ’ s why I support it . “ What God has joined together , let no man put asunder ” is something vital for marriages , but not genes .
Dr . Barry practices Internal Medicine with Norton Community Medical Associates-Barret . She is a clinical associate professor at the University of Louisville School of Medicine , Department of Medicine .
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