Early data has been announced for two trials and the news is disappointing.
US gene-editing biotech, Sangamo Therapeutics, has released interim results from its Phase 1 trial for a treatment in Hunter syndrome, a rare genetic disease. The interest in and reaction to the results has been strong, as this has been the first US trial of a gene-editing therapy in humans.
Sangamo uses its own proprietary gene-editing technology, ZFNs, which is a competitor technology to CRISPR/Cas9 (more on these technologies can be found here).
The main problem with the trial results was efficacy. As measured by the presence of biomarkers after 24 weeks, the treatment seemed to have little effect.
One high-dose patient got a more significant boost but it was short-lived. There is a possibility that this was due to an immune system reaction against the viral vector ((AAV) used to deliver the gene-altering components into cells. To date, AAV vectors haven’t caused serious problems but experts have raised concerns about the safety of AAV vectors when used at high doses.
In the second announcement, Solid Biosciences announced initial 3-month biopsy data from its Phase I/II dose-ascending clinical trial evaluating the safety and efficacy of SGT-001 microdystrophin gene transfer for the treatment of DMD. SGT-001 is a novel AAV vector-mediated gene transfer therapy. The early data showed low levels of microdystrophin protein expression. In fact, the results were even poorer than those achieved previously by Sarepta.
Shares of all U.S. gene therapy companies sank in response to the announcements.
It’s perhaps worthwhile rereading Dr Robert Hayes comments on the potential advantages of CPPs over AAVs in delivery of gene-editing therapies.
The CRISPr/Cas9 field is evolving one. Until March this year, much of the genome was still inaccessible to CRISPr/Cas9 because of DNA sequence requirements. However, David Liu and his team at the Broad Institute have now modified the Cas9 enzyme to remove much of that limitation. The same rapid progress is seen in the delivery of CRISPr/Cas9 into cells. Originally, the process was very inefficient, but the development of viral vectors, nanoparticles, and microinjection techniques are changing that. So, what does Phylogica's FPP technology bring to the table, and why are CRISPr/Cas9 companies talking to us? It’s because, despite progress in this field, the transformation of cells is still complicated, especially if you want to make a lot of changes in the genome. In contrast, attaching an FPP onto Cas9 is an easy process that requires no changes in manufacturing or processing. It’s easy. There’s no complex chemistry, and unlike nanoparticles or viruses, it’s not expensive or difficult, and there are no threats of immunogenicity or toxicity. Indeed, every one of Phylogica’s Cas9-FPP molecules comes with its very own built-in delivery system. But the real advantage of our technology is cell-specificity. We showed in earlier work that we can find FPPs that are specific for certain cells types (e.g., brain endothelial cells). The delivery of CRIPSPr/Cas9 to specific cell types and tissues is a clear and valuable advantage that Phylogica’s FPPs can provide.
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