New RNA stem cell editing reduces unintended genetic complications

The recent paper, "RNA-generated and gene-edited induced Pluripotent Stem Cells for disease modeling and therapy," in the September 13th Issue of the Journal of Cellular Physiology, describes the revolutionary process of reprogramming somatic cells into iPSCs, similar to embryonic stem cells. The authors cite the progress of their research as building on the work of Nobel Laureate Dr. Shinya Yamanaka, which firmly established the practicality of using patient cells to generate potentially any cell type of the human body.

Dr. Ileana Zucchi, Dr. James Kehler, and Dr. Rolland Reinbold at the National Research Council-Institute of Biomedical Technology (CNR-ITB) in Italy collaborated with U.S.-based counterparts at the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University in Philadelphia, including the institute Director, Dr. Antonio Giordano, and group leader Dr. Gianfranco Bellipanni.

While the technology has been available for several years, an imposing and remaining challenge was to not introduce unwanted or unintentional genetic changes into the cells that would prove potentially unsafe or ethically unacceptable.

The more recent and equally important technology using CRISPR/Cas9 system to change genes also shared this limitation that unintended genomic events may potentially make cells unsafe for clinical use.

By using alternative technologies to DNA plasmid or viral vector gene delivery, the researchers were able to make and edit human iPSCs by transient transfection of RNAs with no risk of integration or retention, providing a safer and more clinically relevant approach to modeling human diseases and developing new potential therapies.

"We combined reprogramming and gene-editing using an RNA-based platform to reduce the risks of traditional tools that can interfere with iPSC function and stability," Dr. James Kehler, lead co-author and scientist at the CNR and director of scientific alliances at MTI-GlobalStem explained.

Dr. Zucchi added, "We are grateful for the contributions of our collaborators in industry, Dr. Alice Chen at Organovo and Dr. Miranda Yang at Ascendance Biotechnologies. This collaborative research will promote the generation of custom made functional human tissues and organs through in vitro printing, micro-patterning and bio-engineering. Additionally, drug-target interactions can now be validated more quickly in human iPSC-derived models to screen for drug effectiveness and potential off-target toxicity in panels of patient cells for applications in precision medicine."

Prof. Giordano, contacted in his office in Philadelphia, extolled the value of international collaborations in research as vital for the progress of science, adding, "stem cell research is reaching levels that soon will impact the life of millions people."