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| Type |
Poster Presentation |
| Area |
Life Chemistry |
| Room No. |
Grand Ballroom |
| Time |
10월 19일 (금요일) 11:00~12:30 |
| Code |
LIFE.P-439 |
| Subject |
CRISPR-Cas9-based strategies to alleviate ABCD1 protein deficiency in X-linked adrenoleukodystrophy |
| Authors |
Sung-ah Hong, Jihyeon Yu1, Sangsu Bae2,*
Hanyang University, Korea
1Department of chemistry, Hanyang University, Korea
2Department of Chemistry, Hanyang University, Korea
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| Abstract |
X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease which has variable clinical spectrum and is caused by mutations in the ATP binding cassette subfamily D member 1 (ABCD1) gene. ABCD1 gene encodes ABCD1 protein located in the peroxisomal membrane, and deficiency of ABCD1 protein impairs the peroxisomal beta-oxidation of very long-chain fatty acids (VLCFA). Recently, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) has been widely studied as it holds potential for therapeutic applications. In this study, we utilized CRISPR-Cas9-based strategies to make genetic background possible to express functional ABCD1 protein in ALD patient-derived fibroblasts cells. ssODN donor or an evolved transfer RNA adenosine deaminase fused to a catalytically impaired CRISPR–Cas9 which is known as adenine base editor (ABE) was used to convert a point mutation(c.796G>A, p.Gly266Arg) into normal. Also, we tried to insert ABCD1 cDNA encoding normal ABCD1 protein using non-homologous end joining (NHEJ)-mediated knock-in. As a result, we found that the frequency of ABE-mediated gene correction was higher than that of ssODN-mediated gene correction and confirmed the insertion of ABCD1 cDNA.
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| E-mail |
sahong1122@gmail.com |
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122nd General Meeting of the KCS