Recent Patents on MicroRNA-Induced Pluripotent Stem Cell Generation
Jack S.K. Chen and Shi-Lung Lin
Affiliation: WJWU & LYNN Institute for Stem Cell Research, 12145 Mora Drive, STE6, Santa Fe Springs, CA 90670, USA.
Keywords: DNA demethylation, embryonic stem cell (ESC), induced pluripotent stem cell (iPSC), microRNA (miRNA), miR-
302, microRNA-reprogrammed iPSC (mirPSC), pluripotency, somatic cell reprogramming, Nuclear reprogramming factor, miR-520.
Regenerative medicine using pluripotent stem cells represents the future for curing developmental abnormalities,
degenerative disorders and aging-related illnesses. However, today’s regenerative medicine faces two major challenges
with respect to stem cells: their shortage in supply and uncertain safety in clinical therapy. The recent discovery of
induced pluripotent stem cells (iPS cells or iPSCs) derived from patients’ somatic cells presents a possible solution for the
supply shortage problem. Yet, iPSC generation with the enforced overexpression of previously defined four factors Oct4–
Sox2-Klf4-c-Myc (OSKM) also causes oncogenic stimulation, which leads to potential tumorigenicity. The more recent
development of miR302-mediated iPSC generation may further solve this problem since miR-302, a tiny 23-nucleotide
non-coding microRNA (miRNA), is able to replace all four OSKM in mediating iPSC formation while preventing the onset
of stem cell tumorigenicity. MiR-302-reprogrammed iPSCs (mirPSCs) not only possess a highly demethylated genome
but also share >92% gene expression similarity with human embryonic stem cells (hESCs). Transplantation of mirPSCs
into immunocompromised mice leads to the formation of relatively organized tissue cysts containing various cell types derived
from all three embryonic germ layers (ectoderm, mesoderm and endoderm), providing a potential tool for regenerative
medicine. Hence, this novel iPSC technology offers a simple, effective and safe method for not only reprogramming
somatic cells to hESC-like pluripotent stem cells but also maintaining stem cell pluripotency in tumor-free conditions.
Conceivably, mirPSCs present a more suitable choice of iPSCs based on current Food and Drug Administration (FDA)
regulations. Due to the novelty of this recent technology, a majority of patent applications are still pending and are mainly
led by two major research groups, Lin et al. (WJWU & LYNN Institute - 7 filings) and Yamanaka et al. (Kyoto University
- 3 filings). This review will summarize all relevant patent applications and describe the mechanisms underlying this
new miRNA-mediated iPSC generation technology.
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