Why don't stem cell therapies use a virus to deliver gene editing sequences to stem cells instead of the harvesting-transformation-transplant route.

I thought it might be because of a lack of specificity on the part of the viruses, but then I saw phage display techniques that would seem to make that a non-issue.

I thought it might be trans-cytosis or getting the phages out of the blood-stream and into contact with the stem cells. I haven't found an easy solution to this hurdle, but it doesn't seem to be insurmountable.

I think the main issue is regulatory? Perhaps a lack of precedents in this area. What do you think of my analysis? Is this idea even feasible?

  • $\begingroup$ There is active research in this area using animal models, which bypasses many ethical hurdles (I assume that's what you mean by regulatory). The immune system is a significant hurdle. $\endgroup$
    – canadianer
    Commented Jan 20, 2015 at 21:33
  • $\begingroup$ Phage display isn't that good at making structures that actually work in vivo. I'm not saying there are no successes, but the rate is pretty low. And any time you're delivering viruses into a patient you're likely to develop antibodies against that virus, making repeated doses harder. That's how vaccines work. $\endgroup$
    – user137
    Commented Jan 20, 2015 at 21:40
  • $\begingroup$ Any idea how far along the animal model viruses are? $\endgroup$
    – Dale
    Commented Jan 20, 2015 at 22:08
  • $\begingroup$ Interesting read relating the subject. $\endgroup$
    – CKM
    Commented Jan 20, 2015 at 22:23

2 Answers 2


Stem cell therapies do in fact utilise viruses. In the examples cited, the stem cells were infected by viruses in vitro, genetically modified, and then reintroduced into the target as autologous transplants. The main issue at hand is that live viruses introduced directly would be targeted and destroyed by the immune system, which greatly reduces their efficacy in causing transformation of cells.

In a recent Nature paper, zinc finger nucleases were used to target and disrupt the CCR5 or CXCR4 gene, which greatly reduces the efficiency of HIV binding to CD4+ T cells. The zinc finger nucleases were introduced into the cells using an adenovirus vector.

Generation of cxcr4 ZFN adenovirus and CGW-siX4s lentiviral vectors. The CXCR4 targeting locations of siX4s and ZFN are shown in Supplementary Figure S1.

This technique was then used in a number of clinical trials to modify hematopoietic stem cells using zinc finger nucleases, as summarised in this review paper. The recent advent of CRISPR-Cas systems will probably lead to an increase in similar techniques, due to the higher specificity and ease of engineering of Cas9-based nucleases.

  • $\begingroup$ This is an exciting field. I am very interested in the potential to avoid the immune system. $\endgroup$
    – Dale
    Commented Jan 21, 2015 at 16:32

Thanks to you guys I googled, "stem cell virus animals" and found some promising links! I appreciate you guys emphasizing immunological response. I was hoping that the virus would be effective enough to work on the first shot and thereby avoid most of the immunological complications. However it seems that the second generation of adenovirus vectors in animal models was abandoned for just that reason: source - NCBI.

Here is a nice excerpt regarding animal models:

third-generation adenovirus vectors”: This research focuses on the development of improved production systems for gutless adenovirus vectors and their use for the efficient introduction of large or multiple transgenes into human progenitor and stem cells with minimal vector-related toxicity. In addition to the use of regular third-generation adenovirus vectors for the transient genetic modification of target cells, we have embarked on the generation of new vector types for stable transgene expression in transduced target cells using locus/site-specific transgene integration or homologous recombination. For example, we have generated new adenovirus/adeno-associated virus vectors. These vectors stably integrate into a specific locus on human chromosome 19 and are capable of genetically complementing dystrophin-deficient human myoblasts.

-Leeds Universitair (NZ)


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