دورية أكاديمية
Targeted Gene Editing in Porcine Spermatogonia.
العنوان: | Targeted Gene Editing in Porcine Spermatogonia. |
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المؤلفون: | Webster D; Recombinetics, Inc., St. Paul, MN, United States., Bondareva A; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada., Solin S; Recombinetics, Inc., St. Paul, MN, United States., Goldsmith T; Recombinetics, Inc., St. Paul, MN, United States., Su L; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada., Lara NLEM; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada., Carlson DF; Recombinetics, Inc., St. Paul, MN, United States., Dobrinski I; Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada. |
المصدر: | Frontiers in genetics [Front Genet] 2021 Jan 28; Vol. 11, pp. 627673. Date of Electronic Publication: 2021 Jan 28 (Print Publication: 2020). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101560621 Publication Model: eCollection Cited Medium: Print ISSN: 1664-8021 (Print) Linking ISSN: 16648021 NLM ISO Abbreviation: Front Genet Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Lausanne : Frontiers Research Foundation. |
مستخلص: | To study the pathophysiology of human diseases, develop innovative treatments, and refine approaches for regenerative medicine require appropriate preclinical models. Pigs share physiologic and anatomic characteristics with humans and are genetically more similar to humans than are mice. Genetically modified pigs are essential where rodent models do not mimic the human disease phenotype. The male germline stem cell or spermatogonial stem cell (SSC) is unique; it is the only cell type in an adult male that divides and contributes genes to future generations, making it an ideal target for genetic modification. Here we report that CRISPR/Cas9 ribonucleoprotein (RNP)-mediated gene editing in porcine spermatogonia that include SSCs is significantly more efficient than previously reported editing with TALENs and allows precise gene editing by homology directed repair (HDR). We also established homology-mediated end joining (HMEJ) as a second approach to targeted gene editing to enable introduction of larger transgenes and/or humanizing parts of the pig genome for disease modeling or regenerative medicine. In summary, the approaches established in the current study result in efficient targeted genome editing in porcine germ cells for precise replication of human disease alleles. Competing Interests: DW, SS, TG, DC, and ID are employees and/or shareholders in Recombinetics, Inc., a company that commercializes gene editing in livestock. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Webster, Bondareva, Solin, Goldsmith, Su, Lara, Carlson and Dobrinski.) |
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معلومات مُعتمدة: | R01 HD091068 United States HD NICHD NIH HHS; R01 OD016575 United States OD NIH HHS; R43 GM108150 United States GM NIGMS NIH HHS; R44 GM108150 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: CRISPR/Cas9; gene targeting; homology directed repair; homology-mediated end joining; pig; spermatogonia |
تواريخ الأحداث: | Date Created: 20210215 Latest Revision: 20211230 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7876475 |
DOI: | 10.3389/fgene.2020.627673 |
PMID: | 33584819 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1664-8021 |
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DOI: | 10.3389/fgene.2020.627673 |