It’s a little late to qualify for the 2014 Winter Olympics, but Genome Editing still scored a huge translational gold medal. Deploying Zinc Finger Nuclease (ZFN) genome editing techniques, researchers have edited the CCR5 ‘trojan horse’ receptor that HIV uses to infect our immune system’s vital CD4 T cells.
ZFNs have shown promise with their combination of the DNA recognition specificity of zinc-finger proteins (ZFPs) partnered with “the robust but restrained enzymatic activity” of the DNA devouring FokI. With this dynamic duo, clinical researchers targeted and knocked out their sequence of interest. In this case that tiny editing job gave patients the naturally occurring but ‘magical’ HIV resistant phenotype conferred upon by the famous Δ32 allele.
Here’s what went down:
- 12 HIV patients were enrolled in an open-label, nonrandomized, uncontrolled study of a single dose of ZFN-modified autologous CD4 T cells.
- The primary outcome of safety was assessed by treatment-related adverse events and the secondary outcomes included measures of immune reconstitution and HIV resistance.
- While there was one adverse reaction to the transfusion, the rest of the patients fared better, with HIV RNA becoming undetectable in one of the patients and blood level of HIV DNA in most patients decreasing.
The medical team concluded that “CCR5-modified autologous CD4 T-cell infusions are safe within the limits of this study” and that they were successful in “the partial induction of acquired genetic resistance to HIV infection after targeted gene disruption” by ZFNs. It’s still early in the game, but based on these results, it’s hard not to dream of the potential of a druggable genome.
Check out the Genetic Editing revolution in action over at the New England Journal of Medicine, March 2014