Correction of the pathogenic mutation in TGM1 gene by adenine base editing in mutant embryos
| Autor: | Xiufang Zhong, Xingxu Huang, Hanyan Liu, Xueliang Zhou, Lihua Yuan, Lu Dang, Wuwen Zhang, Guoqing Tong, Wenxia Yu, Shisheng Huang, Jianqiao Liu, Guanglei Li, Lei Li, Yuanyuan Chen |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Heterozygote
Mutant Biology medicine.disease_cause Deep sequencing chemistry.chemical_compound Germline mutation Drug Discovery Genetics medicine Humans Guide RNA Molecular Biology Gene Gene Editing Pharmacology Mutation Transglutaminases Adenine Lamellar ichthyosis medicine.disease chemistry Molecular Medicine Original Article DNA RNA Guide Kinetoplastida |
| Zdroj: | Mol Ther |
| ISSN: | 1525-0016 |
| Popis: | A couple diagnosed as carriers for lamellar ichthyosis, an autosomal recessive rare disease, encountered two pregnancy losses. Their blood samples showed the same heterozygous c.607C>T mutation in the TGM1 gene. However, we found that about 98.4% of the sperm had mutations, suggesting possible de novo germline mutation. To explore the probability of correcting this mutation, we used two different adenine base editors (ABEs) combined with related truncated single guide RNA (sgRNA) to repair the pathogenic mutation in mutant zygotes. Our results showed that the editing efficiency was 73.8% for ABEmax-NG combined with 20-bp-length sgRNA and 78.7% for Sc-ABEmax combined with 19-bp-length sgRNA. The whole-genome sequencing (WGS) and deep sequencing analysis demonstrated precise DNA editing. This study reveals the possibility of correcting the genetic mutation in embryos with the ABE system. |
| Databáze: | OpenAIRE |
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