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

Mira Cho, Kwangsoo Jung, Seung Hyun Kim, Il Sun Kim, Miri Kim, Mikyung Shin, Haeshin Lee, Kook In Park, Jae Hyung Jang

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)135-150
Number of pages16
JournalGene Therapy
Volume26
Issue number5
DOIs
Publication statusPublished - 2019 May 1

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Dependovirus
Neural Stem Cells
Interleukin-10
Safety
Virus Diseases
Genes
Cell- and Tissue-Based Therapy
Brain Infarction
Therapeutics
Nervous System Diseases
Transgenes
Genetic Therapy
Brain Injuries
Suspensions
Stem Cells
Animal Models
Technology
Gene Expression
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Cho, Mira ; Jung, Kwangsoo ; Kim, Seung Hyun ; Kim, Il Sun ; Kim, Miri ; Shin, Mikyung ; Lee, Haeshin ; Park, Kook In ; Jang, Jae Hyung. / Safety and efficacy evaluations of an adeno-associated virus variant for preparing IL10-secreting human neural stem cell-based therapeutics. In: Gene Therapy. 2019 ; Vol. 26, No. 5. pp. 135-150.
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Safety and efficacy evaluations of an adeno-associated virus variant for preparing IL10-secreting human neural stem cell-based therapeutics. / Cho, Mira; Jung, Kwangsoo; Kim, Seung Hyun; Kim, Il Sun; Kim, Miri; Shin, Mikyung; Lee, Haeshin; Park, Kook In; Jang, Jae Hyung.

In: Gene Therapy, Vol. 26, No. 5, 01.05.2019, p. 135-150.

Research output: Contribution to journalArticle

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