RNA Virus-Based Episomal Vector with a Fail-Safe Switch Facilitating Efficient Genetic Modification and Differentiation of iPSCs

A gene delivery system that allows efficient and safe stem cell modification is critical for next-generation stem cell therapies. An RNA virus-based episomal vector (REVec) is a gene transfer system developed based on Borna disease virus (BoDV), which facilitates persistent intranuclear RNA transgene delivery without integrating into the host genome. In this study, we analyzed susceptibility of human induced pluripotent stem cell (iPSC) lines from different somatic cell sources to REVec, along with commonly used viral vectors, and demonstrated highly efficient REVec transduction of iPSCs. Using REVec encoding myogenic transcription factor MyoD1, we further demonstrated potential application of the REVec system for inducing differentiation of iPSCs into skeletal muscle cells. Of note, treatment with a small molecule, T-705, completely eliminated REVec in persistently transduced cells. Thus, the REVec system offers a versatile toolbox for stable, integration-free iPSC modification and trans-differentiation, with a unique switch-off mechanism.

• Publication year

  2019

• Venue

  Molecular Therapy: Methods & Clinical Development

• Publication date

  2019-05-28

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.omtm.2019.05.010PMID 31309127PMCID 6606997
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Degradation of amyloid β peptide by neprilysin expressed from Borna disease virus vector

  2018cited by this paper
• Making muscle: skeletal myogenesis in vivo and in vitro

  2017cited by this paper
• Antiviral activity of favipiravir (T‐705) against mammalian and avian bornaviruses

  2017cited by this paper
• Long-term expression of miRNA for RNA interference using a novel vector system based on a negative-strand RNA virus

  2016cited by this paper
• B-108 Specific HIV integration sites are linked to clonal expansion and persistence of infected cells

  2016cited by this paper
• A novel intranuclear RNA vector system for long-term stem cell modification

  2015influential reference
• An siRNA Screen Identifies the U2 snRNP Spliceosome as a Host Restriction Factor for Recombinant Adeno-associated Viruses

  2015cited by this paper
• Therapeutic genome editing: prospects and challenges

  2015cited by this paper
• Effectiveness of gene delivery systems for pluripotent and differentiated cells

  2015cited by this paper
• Specific HIV integration sites are linked to clonal expansion and persistence of infected cells

  2014cited by this paper
• Myogenic Differentiation of Muscular Dystrophy‐Specific Induced Pluripotent Stem Cells for Use in Drug Discovery

  2014cited by this paper
• Uncovering and dissecting the genotoxicity of self-inactivating lentiviral vectors in vivo.

  2014cited by this paper
• Comprehensive analysis of endogenous bornavirus-like elements in eukaryote genomes

  2013cited by this paper
• Biosafety Features of Lentiviral Vectors

  2013cited by this paper
• Efficient and Reproducible Myogenic Differentiation from Human iPS Cells: Prospects for Modeling Miyoshi Myopathy In Vitro

  2013cited by this paper
• Transplantation of Genetically Corrected Human iPSC-Derived Progenitors in Mice with Limb-Girdle Muscular Dystrophy

  2012cited by this paper
• Development of Sendai Virus Vectors and their Potential Applications in Gene Therapy and Regenerative Medicine

  2012cited by this paper
• Transgene‐Free Disease‐Specific Induced Pluripotent Stem Cells from Patients with Type 1 and Type 2 Diabetes

  2012cited by this paper
• Myoblasts Derived From Normal hESCs and Dystrophic hiPSCs Efficiently Fuse With Existing Muscle Fibers Following Transplantation

  2012cited by this paper
• Bornavirus closely associates and segregates with host chromosomes to ensure persistent intranuclear infection.

  2012influential reference
• A Novel Borna Disease Virus Vector System That Stably Expresses Foreign Proteins from an Intercistronic Noncoding Region

  2011cited by this paper
• Development of Defective and Persistent Sendai Virus Vector

  2010influential reference
• Characterization of Retroviral and Lentiviral Vectors Pseudotyped with Xenotropic Murine Leukemia Virus-Related Virus Envelope Glycoprotein

  2010cited by this paper
• Episomal vectors for gene therapy.

  2008cited by this paper
• Persistent and Stable Gene Expression by a Cytoplasmic RNA Replicon Based on a Noncytopathic Variant Sendai Virus*

  2007cited by this paper
• Cyclosporine Increases Human Immunodeficiency Virus Type 1 Vector Transduction of Primary Mouse Cells

  2006cited by this paper
• Dynamic DNA Methylation and Histone Modifications Contribute to Lentiviral Transgene Silencing in Murine Embryonic Carcinoma Cells

  2005cited by this paper
• Persistent, non‐cytolytic infection of neurons by Borna disease virus interferes with ERK 1/2 signaling and abrogates BDNF‐induced synaptogenesis

  2004cited by this paper
• Progress and problems with the use of viral vectors for gene therapy

  2003cited by this paper
• Borna disease virus: new aspects on infection, disease, diagnosis and epidemiology.

  2000cited by this paper
• Expression of a single transfected cDNA converts fibroblasts to myoblasts.

  1987cited by this paper

• Episomal Vectors: Principle, Utility, and Application

  2025cites this paper
• Scalable control of stem cell fate by riboswitch-regulated RNA viral vector without genomic integration

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• Genetically modified organoids for tissue engineering and regenerative medicine.

  2024cites this paper
• Development of an RNA virus-based episomal vector with artificial aptazyme for gene silencing

  2024cites this paper
• Viral Replicon Systems and Their Biosafety Aspects

  2023cites this paper
• Genetically modified cell spheroids for tissue engineering and regenerative medicine.

  2023cites this paper
• Efficacy of oligodendrocyte precursor cells as delivery vehicles for single-chain variable fragment to misfolded SOD1 in ALS rat model

  2023cites this paper
• Reverse Genetics and Artificial Replication Systems of Borna Disease Virus 1

  2022cites this paper
• Stability of Borna disease virus‐based episomal vector under physical and chemical stimulation

  2021cites this paper
• Human muscle production in vitro from pluripotent stem cells: Basic and clinical applications.

  2021cites this paper
• Genetically modified cell sheets in regenerative medicine and tissue engineering.

  2021cites this paper
• The Borna Disease Virus 2 (BoDV-2) Nucleoprotein Is a Conspecific Protein That Enhances BoDV-1 RNA-Dependent RNA Polymerase Activity

  2021cites this paper
• Optimal Expression of the Envelope Glycoprotein of Orthobornaviruses Determines the Production of Mature Virus Particles

  2020cites this paper
• Reverse genetics approaches of Borna disease virus: applications in development of viral vectors and preventive vaccines.

  2020cites this paper
• Production of high‐titer transmission‐defective RNA virus‐based episomal vector using tangential flow filtration

  2020cites this paper
• In vivo biodistribution analysis of transmission competent and defective RNA virus-based episomal vector

  2020cites this paper
• Development of an RNA Virus-Based Episomal Vector Capable of Switching Transgene Expression

  2019cites this paper