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Safety and efficacy evaluations of an adeno-associated virus variant for preparing IL10-secreting human neural stem cell-based therapeutics

Gene Therapy (2019) | Download Citation


Gene therapy technologies are inevitably required to boost the therapeutic performance of cell therapies; thus, validating the efficacy of gene carriers specifically used for preparing cellular therapeutics is a prerequisite for evaluating the therapeutic capabilities of gene and cell combinatorial therapies. Herein, the efficacy of a recombinant adeno-associated virus derivative (rAAVr3.45) was examined to evaluate its potential as a gene carrier for genetically manipulating interleukin-10 (IL10)-secreting human neural stem cells (hNSCs) that can potentially treat ischemic injuries or neurological disorders. Safety issues that could arise during the virus preparation or viral infection were investigated; no replication-competent AAVs were detected in the final cell suspensions, transgene expression was mostly transient, and no severe interference on endogenous gene expression by viral infection occurred. IL10 secretion from hNSCs infected by rAAVr3.45 encoding IL10 did not alter the transcriptional profile of any gene by more than threefold, but the exogenously boosted IL10 was sufficient to provoke immunomodulatory effects in an ischemic brain injury animal model, thereby accelerating the recovery of neurological deficits and the reduction of brain infarction volume. This study presents evidence that rAAVr3.45 can be potentially used as a gene carrier to prepare stem cell therapeutics.

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This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning (MSIP) (2018R1A2A2A05020786), the Bio&Medical Technology Development Program of NRF funded by the Korean government, MSIP (2017M3A9B4061968), and the grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C1564 & HI16C1089).

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The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

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  1. These authors contributed equally: Mira Cho, Kwangsoo Jung


  1. Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, 03722, Korea

    • Mira Cho
    • , Seung-Hyun Kim
    •  & Jae-Hyung Jang
  2. Department of Pediatrics, College of Medicine, Yonsei University, Seoul, 03722, Korea

    • Kwangsoo Jung
    • , Il-Sun Kim
    • , Miri Kim
    •  & Kook In Park
  3. Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea

    • Mikyung Shin
    •  & Haeshin Lee
  4. Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA

    • Mikyung Shin


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Correspondence to Kook In Park or Jae-Hyung Jang.

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