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Utilization of CRISPR/Cas9-Mediated ...

Wong, Tatianna Wai Ying.

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Utilization of CRISPR/Cas9-Mediated Gene Editing for Correction of Deletion Mutations in DMD.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Utilization of CRISPR/Cas9-Mediated Gene Editing for Correction of Deletion Mutations in DMD./
作者:	Wong, Tatianna Wai Ying.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
面頁冊數:	112 p.
附註:	Source: Dissertations Abstracts International, Volume: 82-06, Section: B.
Contained By:	Dissertations Abstracts International82-06B.
標題:	Genetics. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28148549
ISBN:	9798698550273

Utilization of CRISPR/Cas9-Mediated Gene Editing for Correction of Deletion Mutations in DMD.
Wong, Tatianna Wai Ying.

Utilization of CRISPR/Cas9-Mediated Gene Editing for Correction of Deletion Mutations in DMD. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 112 p.

Source: Dissertations Abstracts International, Volume: 82-06, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2020.

This item must not be sold to any third party vendors.

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder that affects 1 in 5000 boys. DMD is caused by the absence of dystrophin due to mutations in the DMD gene, leading to compromised muscle fiber integrity and progressive muscle deterioration. Deletion mutations account for almost 70% of the DMD mutation spectrum, where the DMD open reading frame (ORF) is disrupted, resulting in the absence of dystrophin expression. In developing a mouse model representative of the DMD disease progression, the first mouse model carrying a Dmd deletion of exons 52-54 (Dmd D52-54) was generated. Dmd D52-54 lacks dystrophin, resulting in dystrophic pathophysiology, cardiac hypertrophy and tachycardia. Removal of exon 55 in the Dmd D52-54 model is expected to yield an in-frame deletion of Dmd exons 52-55 (Dmd D52-55), which is representative of the milder Becker muscular dystrophy (BMD). Through phenotypic characterization, the Dmd D52-55 mouse model validates that the in-frame deletion produces a functional dystrophin protein which improves disease manifestation. To reproduce the Dmd D52- 55 mutational outcome in Dmd D52-54, CRISPR/Cas9 was used to restore the Dmd ORF by either deleting exon 55 or disrupting exon 55 inclusion by targeting a splice site. The strategy was further improved by increasing the dosage of sgRNAs, which led to the recovery of truncated dystrophin protein in the heart and skeletal muscle as well as mild functional improvement. Optimization in sgRNA dosage will be implemented to enhance the efficiency of dystrophin restoration using CRISPR-mediated single sgRNA exon skipping, providing a potential new therapeutic avenue for DMD caused by deletion mutations.

ISBN: 9798698550273Subjects--Topical Terms:

530508
Genetics.
Subjects--Index Terms:

Neuromuscular disorder

Utilization of CRISPR/Cas9-Mediated Gene Editing for Correction of Deletion Mutations in DMD.
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