Restored Low Density Lipoprotein Uptake in Gene-corrected iPSC-derived Hepatocytes from Homozygous Familial Hypercholesterolemia

Research Project

Project/Area Number	15K19508
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Metabolomics
Research Institution	Kanazawa University
Principal Investigator	Okada Hirofumi 金沢大学, 医学系, 協力研究員 (10735161)
Project Period (FY)	2015-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	iPS細胞 / CRISPR/Cas9 / 再生医療 / 代謝学 / 代謝
Outline of Final Research Achievements	To examine whether LDLR function of HLCs from genetically-corrected iPSCs can be restored in human, iPSCs were generated from a HoFH patient harboring a point mutation (c.901G>T) in exon 6 of LDLR, which impairs LDL uptake. We generated one homozygous gene-corrected HoFH-iPSC clone and two heterozygous gene-corrected HoFH-iPSC clones using the CRISPR/Cas9 system. Subsequently, we obtained functionally corrected HLCs with significantly recovered LDL uptake ability compared to those without gene correction. Under these conditions, few immunological rejections were observed by cell-mediated cytotoxicity assay.