Human trial demonstrates the longevity of CRISPR-edited transplanted cells

gene editing human cells

Date: 16th September 2019

An attempt to use CRISPR genome-edited donor cells to treat a HIV patient with blood cancer for the first time.

The gene-editing field is buzzing at the hope that CRISPR-derived applications may translate into the clinic as powerful agents to combat disease and genetic disorders.

Whilst it is clear there is huge potential for CRISPR-therapies, there is still little available data to determine just how successful these will be at translating into human medicines.

Now scientists in China have used hematopoietic stem and progenitor cells (HSPCs) edited with CRISPRs to try and cure HIV in a 27 year old patient with Acute Myeloid Leukaemia (AML).

CCR5 gene

The CCR5 gene encodes the major HIV co-receptor that allows viral entry into the host cells.  It has been the source of several breakthroughs in the hunt for a HIV cure.

  • One of the earlier indications that CCR5 played a role in HIV in humans occurred when two patients, one from Berlin and the other from London, were ‘cured’ of HIV when they received routine stem cell transplants after chemotherapy for acute myeloid leukaemia (AML).  Unknown at the time, the donor cells came from individuals who were naturally resistant to HIV due to the presence of a genetic mutation in the CCR5 gene.
  • Researchers at the Aaron Diamond AIDS Research Center, Rockefeller University, New York found that this HIV co-receptor accounts for the resistance of some individuals to HIV and individuals with a homozygous internal 32 base pair deletion (CCR5 delta32) were resistant to HIV-1.
  • Individuals heterozygous for CCR5 delta32 have also been shown to have a slower HIV disease progression to AIDS.
  • Sangamo Therapeutics Inc. Richmond, California, have further built on this work by designing Zinc Finger Nuclease (ZFN) assemblies to specifically target CCR5 and, amongst other things, have demonstrated that human haematopoietic/stem cell progenitors were able to repopulate NOD-SCID mice challenged with HIV-1.

However, the availability of naturally occurring HIV-resistant donors with HLA-compatibility is a limiting factor when looking at donor transplantation as a broader treatment regime for patients with HIV.

Now researchers have turned to gene-editing technology for the solution.  Emulating the London and Berlin cases, they have ablated the CCR5 gene in HSPCs using CRISPR-Cas9 and transplanted them into a patient diagnosed with AML and HIV, following chemotherapy treatment.

The results of the study have been mixed…

Successful transplantation and long-term engraftment of CRISPR-edited HSPCs was seen.  The CRISPR-edited cells persisted in the patient’s blood for the duration of a 19 month observation period, and no off-target effects were observed.

However, the efficiency of editing events was low (around 17%) and, once transplanted, only 5-8% of the stem cell progeny contained the CCR5 edit.  In this case, the levels of HIV were not reduced, although the cancer did remain in remission.

The observation that gene-edited cells can be detected a considerable time post-transplantation is an exciting result.  The mere fact that the patient has survived with no apparent side-effects caused by the treatment may also alleviate some safety concerns.

Whether the lack of off-targets effects is due to the low number of CCR5-edited cells being present remains to be answered, and to achieve a more effective HIV treatment higher percentages of edited cells most certainly will be needed. Further optimisation to increase editing efficiency is also clearly an important next step in the process.

genetic engineering

The use of CRISPRs in Humans

Stories emerging from China last year, reported the birth of the first CRISPR gene-edited babies.  Again the edits in question were designed to offer HIV-resistance, once again the target CCR5.

The experiments, performed by He Jiankui and his team, were widely condemned and surrounded by ethical uproar. Amongst other things, CCR5 plays a role in the brain and cognition and in 2016, Zhou and his colleagues showed that decreasing the CCR5 function in mice enhanced memory posing the question of whether ‘CRISPR humans’ could develop enhanced brain function or even super-intelligence.

So taking all this into consideration, whilst the results of this most recent study may show progress from a technical perspective about translation into the clinic, there is work to do from an efficacy standpoint.

Furthermore, a clear cautionary note continues to be posed when we consider the potential broader biological and ethical questions that this study and others like it are increasingly asking us to think about.  With the accessibility and applications of CRISPRs so readily available, the responsibility falls into all of our hands.


Xu, L., J. Wang, Y. Liu, L. Xie, B. Su, D. Mou, L. Wang, T. Liu, X. Wang, B. Zhang, L. Zhao, L. Hu, H. Ning, Y. Zhang, K. Deng, L. Liu, X. Lu, T. Zhang, J. Xu, C. Li, H. Wu, H. Deng and H. Chen (2019). “CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia.” New England Journal of Medicine 381(13): 1240-1247.