After the big scandal of the CRISPR babies at the end of 2018, some might have thought that would be the end of CRISPR in the clinic, but luckily that has not been the case and despite the public outrage of last year, today we can report 1 on its successful use as gene therapy against AIDS. Let’s see how it was done. In 2008 we learned about the first person in history to be cured from AIDS, the so-called Berlin patient stopped taking his antiretroviral drugs and instead received a bone marrow transplant from a donor with a natural mutation in the CCR5 gene. As a result the patient was not only cured of AIDS but also of leukaemia. In this case, and similarly to the CRISPR babies, the edited gene was also the CCR5 gene which, when mutated in both copies, inhibits the entrance of the VIH virus into lymphocytes. The 27-year-old patient had not only HIV but also acute lymphoblastic leukemia. Using CRISPR, they edited the DNA of stem cells from his own bone marrow to incapacitate the CCR5 gene. Later, after removing the patient’s own bone marrow they replaced it with the aforementioned edited stem cells intravenously.
More than a year and a half after the treatment the patient’s leukemia is in remission and there are no apparent side effects from the treatment: the gene-edited cells are still around (even if only 5% of all white cells carried the edited gene variant), there were no unwanted DNA changes and the whole procedure seems to be safe. So far so good. However, they were unable to reduce levels of HIV and therefore the patient still needs his antiretroviral medication), which is not surprising looking at the small numbers of edited cells and the fact that only in homozygosis does the inactivation of CCR5 result in HIV-resistant lymphocytes. Let’s just consider this case a proof of principle, that shows that a gene therapy with CRISPR will be possible in the future. Moreover, it is likely that improving the efficiency would help terminate with the virus. Hurray for CRISPR and for the future of personalised genetics! But let’s not forget that we are still far from it being a reality on our doorstep or it being a one-for-all pill. Obviously, CRISPR would preferably work for gene related diseases associated with a SINGLE gene, and of those there are but a few.
Xu et al (2019) CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia. N Engl J Med. 2019 Sep 11. doi: 10.1056/NEJMoa1817426↩