Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 박현정 | - |
dc.date.accessioned | 2022-03-17T06:56:11Z | - |
dc.date.available | 2022-03-17T06:56:11Z | - |
dc.date.issued | 2021-12 | - |
dc.identifier.citation | NPJ REGENERATIVE MEDICINE, Page. 0-0 | en_US |
dc.identifier.issn | 20573995 | - |
dc.identifier.uri | https://www.proquest.com/docview/2621100814?accountid=11283 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/169150 | - |
dc.description.abstract | Huntington’s disease (HD) is a severe inherited neurological disorder caused by a CAG repeat expansion in the huntingtin gene (HTT), leading to the accumulation of mutant huntingtin with polyglutamine repeats. Despite its severity, there is no cure for this debilitating disease. HTT lowering strategies, including antisense oligonucleotides (ASO) showed promising results very recently. Attempts to develop stem cell-based therapeutics have shown efficacy in pre-clinical HD models. Using an HD patient’s autologous cells, which have genetic defects, may hamper therapeutic efficacy due to mutant HTT. Pretreating these cells to reduce mutant HTT expression and transcription may improve the transplanted cells’ therapeutic efficacy. To investigate this, we targeted the SUPT4H1 gene that selectively supports the transcription of long trinucleotide repeats. Transplanting SUPT4H1-edited HD-induced pluripotent stem cell-derived neural precursor cells (iPSC-NPCs) into the YAC128 HD transgenic mouse model improved motor function compared to unedited HD iPSC-NPCs. Immunohistochemical analysis revealed reduced mutant HTT expression without compensating wild-type HTT expression. Further, SUPT4H1 editing increased neuronal and decreased reactive astrocyte differentiation in HD iPSC-NPCs compared to the unedited HD iPSC-NPCs. This suggests that ex vivo editing of SUPT4H1 can reduce mutant HTT expression and provide a therapeutic gene editing strategy for autologous stem cell transplantation in HD. | en_US |
dc.description.sponsorship | This work was supported by Korean Health Technology R&D Project (NRF2017M3A9B4061407, NRF-2018R1C1B6008671, 2018M3A9H3020844) from the National Research Foundation of Korea as well as internal funding from iPS Bio, Inc. | en_US |
dc.language.iso | en | en_US |
dc.publisher | NATURE RESEARCH | en_US |
dc.subject | mutant huntingtin | en_US |
dc.subject | striatal astrocytes | en_US |
dc.subject | expression | en_US |
dc.subject | allele | en_US |
dc.subject | transcription | en_US |
dc.subject | SPT4 | en_US |
dc.subject | neurotransplantation | en_US |
dc.subject | differentiation | en_US |
dc.subject | transplantation | en_US |
dc.subject | elongation | en_US |
dc.title | SUPT4H1-edited stem cell therapy rescues neuronal dysfunction in a mouse model of Huntington’s disease | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1038/s41536-021-00198-0 | - |
dc.relation.page | 0-0 | - |
dc.relation.journal | NPJ REGENERATIVE MEDICINE | - |
dc.contributor.googleauthor | Park, Hyun Jung | - |
dc.contributor.googleauthor | Han, Areum | - |
dc.contributor.googleauthor | Kim, Ji Yeon | - |
dc.contributor.googleauthor | Choi, Jiwoo | - |
dc.contributor.googleauthor | Bae, Hee Sook | - |
dc.contributor.googleauthor | Cho, Gyu-Bon | - |
dc.contributor.googleauthor | Shin, Hyejung | - |
dc.contributor.googleauthor | Shin, Eun Ji | - |
dc.contributor.googleauthor | Lee, Kang-In | - |
dc.contributor.googleauthor | Kim, Seokjoong | - |
dc.contributor.googleauthor | Lee, Jae Young | - |
dc.contributor.googleauthor | Song, Jihwan | - |
dc.relation.code | 2021004026 | - |
dc.sector.campus | E | - |
dc.sector.daehak | RESEARCH INSTITUTE[E] | - |
dc.sector.department | INSTITUTE OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY | - |
dc.identifier.pid | pphj0105 | - |
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