RESUMO
This article has been withdrawn by Aiman Alhazmi, Marissa Mack, Tiffany Rolle, Jordan Hiegel, Syed Haqqani, Nga Dao, Farheen Zaman, Nak-Kyeong Kim, Neel Scarsdale, Charles Lyons, and Joseph Landry. Some of the genome-wide data sets were flawed and were not analyzed correctly. The withdrawing authors are in the process of correcting the data sets and re-analyzing them for resubmission.
RESUMO
Recombinant adeno-associated virus (AAV) vectors are transforming therapies for rare human monogenic deficiency diseases. However, adaptive immune responses to AAV and its limited DNA insert capacity, restrict their therapeutic potential. HEDGES (high-level extended duration gene expression system), a nonviral DNA- and liposome-based gene delivery platform, overcomes these limitations in immunocompetent mice. Specifically, one systemic HEDGES injection durably produces therapeutic levels of transgene-encoded human proteins, including FDA-approved cytokines and monoclonal antibodies, without detectable integration into genomic DNA. HEDGES also controls protein production duration from <3 weeks to >1.5 years, does not induce anti-vector immune responses, is reexpressed for prolonged periods following reinjection, and produces only transient minimal toxicity. HEDGES can produce extended therapeutic levels of multiple transgene-encoded therapeutic human proteins from DNA inserts >1.5-fold larger than AAV-based therapeutics, thus creating combinatorial interventions to effectively treat common polygenic diseases driven by multigenic abnormalities.