Research ArticleGene Therapy

Phagocytosis-shielded lentiviral vectors improve liver gene therapy in nonhuman primates

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Science Translational Medicine  22 May 2019:
Vol. 11, Issue 493, eaav7325
DOI: 10.1126/scitranslmed.aav7325

Vectors in stealth mode

Gene therapy using adeno-associated viral vectors (AAVs) has shown safety and efficacy in patients with hemophilia. However, AAVs have limitations hindering their efficacy in a subgroup of patients. The use of lentiviral vectors (LVs) has been explored as possible alternative; however, preclinical data reported low transduction efficacy possibly due to fast clearance by phagocytes. Now, Milani et al. developed a shielded LV able to escape phagocytosis by increasing the content of the phagocytosis inhibitor CD47 on their surface. Upon intravenous administration in monkeys, the LVs showed high transduction efficacy without signs of toxicity. The results suggest that LV-mediated gene therapy might be an effective strategy for treating hemophilia and possibly other disorders.

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