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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

Measles virus vector offers a new reprogramming platform for iPSC generation

Mayo clinic researchers demonstrate the potential of using measles virus vector as a new one-step reprogramming platform for induced pluripotent stem cell (iPSC) generation.

iPSCs hold great promise for clinical applications in regenerative medicine. Integration-free iPSCs are a pre-requisite for stem cell therapy and this would require using non-integration gene delivery systems such as Sendai virus, recombinant proteins, synthetic mRNA, and episomal vectors.

One of the major obstacles during iPSC generation is the use of multiple (three to six) components which produces partially reprogrammed cells and this in turn reduces the efficiency of the systems.

In the present study published in Gene Therapy, Dr Patricia Devaux and team at Mayo Clinic College of Medicine used a one-step approach in measles virus vector to generate integration-free iPSCs.

Measles virus is a a non-integrating RNA virus that has a long-standing safety record in humans. Preclinical studies have shown its efficacy as a vaccine vector and currently four clinical trials are underway for HIV and Chikungunya viruses.

By substituting the viral attachment protein gene with the green fluorescent protein, the team generated a highly efficient multi-transgene measles virus vector delivery system. Introducing the four reprogramming factors OCT4, SOX2, KLF4, and cMYC via a single, “one-cycle” measles virus vector efficiently reprogrammed human somatic cells into iPSCs. Importantly, measles virus vector genomes were rapidly eliminated in derived iPSCs.

The study demonstrates the potential of measles virus vector as a new reprogramming platform for genomic modification-free iPSCs amenable for clinical translation.

Source: Measles vector as a multiple genes delivery platform facilitating iPSC reprogramming. Wang Q et al., Gene Therapy, February 2019. DOI

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