Korean J Transplant.  2020 Dec;34(Supple 1):S131. 10.4285/ATW2020.OR-1068.

Non-viral ex vivo therapeutic strategy in chemically derived hepatic progenitor with adenine base editor and prime editor

• Kim Y
• Yoon S
• Kim MH
• Hong DH
• Kim T
• Jeong J
• Choi D

• KMID: 2509321
• DOI: http://doi.org/10.4285/ATW2020.OR-1068

Abstract

Background
The adenine base editor (ABE) and prime editing converts nucleotide in living cells without double strand DNA breaks. Chemically derived stem/progenitor cells are attracting attention as the most applicable cell sources for clinical trials. Combining these attracting techniques, we show an ex vivo therapeutic strategy to treat hereditary disease.
Methods
We generate chemically derived hepatic progenitors (CdHs) from a tyrosinemia mouse model caused by a mutation in base pair A into G, correcting it via ABE and prime editing, and then transplanting it into the model mouse to cure it.
Results
Corrected CdHs with ABE repopulated the liver with fumarylacetoacetate hydrolase-positive cells after transplantation and increased survival rate. In addition, the substitution of non-target A in ABE editing window of the CdHs is reduced after transplantation.
Conclusions
This strategy offers a safer and specific way to apply a base editor to clinical applications.