CRISPR-Edited Stem Cells as a Potential Therapeutic Target for Cancer in Immunocompromised Individuals

Simran Kaur ‘20

Figure 1. HIV is a virus that attacks CD4 cells, a special type of white blood cell resulting in a weakened immune system. 

CRISPR-Cas9 technology has been used to edit the mammalian genome for decades, allowing scientists to remove, add, and change sections of DNA sequences. The human immunodeficiency virus (HIV) does not have a cure that exists, but studies have shown that allogeneic transplantation of STEM cells into diagnosed patients can eradicate the virus. CCR5 is the coreceptor for the entry of HIV into cells, and therefore it was hypothesized HSPC’s with an artificial mutation at its locus could help develop HIV resistance in cells.  Scientists in this study transplanted CCR5-edited hematopoietic stem and progenitor cells (CD34+ HSPCs) into a 27-year-old individual diagnosed with HIV-1 and acute lymphoblastic leukemia. 

CD34+ HSPCs from a healthy individual expressing an unmutated CCR5 gene were transplanted into the subject after undergoing total body irradiation at a dose of approximately 5.0 Gy per day. The cells were sorted and subjected to CRISPR insertions and deletions at the CCR5 locus prior to transplantation. After sorting, culturing, and transfection with the ribonucleoprotein complex containing the Cas9 protein, the CCR5-edited CD34+ and CD34- cells were co-infused into the patient, along with the immunosuppressant cyclosporine and antiretroviral drug lopinavir-ritonavir, which were continuing drugs for the patient.

Sanger genome sequencing was used to determine the efficacy of the transplant using the recipient’s bone marrow cells. Assays showed that leukocytes and lymphocyte counts increased following transplantation, and blood platelet and CD4+ cell counts stabilized. The recipient’s acute lymphoblastic leukemia was in complete remission by four weeks after initial transplantation and continued in remission for the following nineteen months. Morphological results from the study show that allogeneic transplantation of CRISPR-edited HSPCs in patients concurrently diagnosed with HIV and leukemia can help achieve remission of leukemia. The clinical safety of CRISPR-Cas9 mediated genome editing was also established because researchers took precautions in introducing the edited cells to the recipient. The results show that the efficacy of HSPC’s as an antiretroviral drug was not sufficient in this study because there was not a significant increase in CD4+ cell count.  Future studies would be beneficial to determine the potential of CRISPR-edited HSPCs as a treatment for individuals diagnosed with HIV-1. 



  1. L. Xu, et al., CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia. NEJM, (2019). doi: 10.1056/NEJMoa1817426
  2. Image retrieved from:

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