Year 3

Reprogramming patient’s adult cells into embryonic-like cells (iPSCs) holds great potential in regenerative medicine, drug screening, and treatment of many diseases, including Alzheimer’s disease, Parkinson’s disease, cardiovascular disease, diabetes, and amyotrophic lateral sclerosis (ALS). However, many technical issues remain before the promise offered by iPSC technology can be realized fully in clinics, including the safety issue using viruses to induce iPSCs. Furthermore, the reprogramming process by existing approaches is too inefficient, forming barriers to translate this technology into clinical studies.

In the third grant year, we have made significant progresses to robustly generate virus-free iPSCs using RNA approaches. We constructed vectors carrying synthetic iPSC-inducing factors that have been engineered in our lab based on the mechanism underlying somatic cell reprogramming. Using both modified RNA and self-replicative RNA cocktails, we delivered the engineered factors into skin cells and efficiently generate iPSCs. Most importantly, due to the high potency of the engineered factor, we were able to generate iPSCs using a single engineered factor, instead of using conventional four factors. Finally, to demonstrate the potential of our engineered factors, we used a Cas9 gene editing method to modify HIV co-receptor CCR5 and created HIV-resistant iPSCs. The iPSC clones derived from the engineered factor RNA exhibited the potency to differentiate into various tissue types. We believe that this engineered factor RNA approach will ultimately become a valuable tool in developing patient-based stem cells for regenerative therapy.