801. Gene Therapy and Transfer: Gene Therapies for Non-Malignant Disorders

Conclusion cited from the abstract:  The preliminary results from our phase I/II study compare favorably with the standard of care in terms of safety and efficacy, and highlight the potential of genetic engineering of HSPC grafts for therapeutic gain-of-function.

 

608

Harry L. Malech,  et al. 

Conclusion cited from the abstract: We observed significantly improved measures of early clinical outcomes from lentivector gene therapy of older children and young adults with X-SCID using enhanced transduction procedure with addition of LentiBoost and dmPGE2, that achieves much greater transduction efficiencies with >10 fold less vector, and results in faster immune reconstitution and more significant clinical benefit by 3 months. The patients are monitored closely for potential risks from higher VCNs that may be balanced by reduced selection pressure due to the greater numbers of gene corrected clones.

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Conclusion cited from the abstract: We developed a rhesus β-to-βs globin conversion model with HSC-targeted genome editing strategies. The gene-edited rhesus CD34+ cells are engraftable for at least 3 months post-transplant. Although further follow-up is necessary for transplanted animals, these findings are helpful in designing HSC-targeted gene correction trials.

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610

Conclusion cited from the abstract: We have developed a tool CD117 ADC that shows potent activity on NHP CD34+ cells. This optimized CD117-ADC is fully myeloablative with a single dose in NHPs, has a favorable safety profile, spares the immune system and is cleared rapidly as designed. In a rhesus model of autologous gene modified HSCT, a single dose of the ADC enables engraftment of auto-gene modified HSC. These proof of concept studies validate the use of CD117-ADC for targeted HSPC depletion prior to transplant and support its use as a new conditioning agent for autologous gene modified HSCT. This targeted approach for safer conditioning could improve the risk benefit profile for patients undergoing stem cell transplant and enable more patients to benefit from these potentially curative therapies.

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611

Conclusion cited from the abstract: 

Overall, these studies demonstrate long-term sustained FVIII expression for up to 10 years with clonal expansion, but without clinical adverse events after AAV-mediated gene therapy for hemophilia.
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612

Conclusion cited from the abstract: Together these results demonstrate, to our knowledge for the first time, the potential of RNP base editing of human HSPCs as an alternative to nuclease editing for HSC-targeted therapeutic genome modification.