{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:04:19Z","timestamp":1789758259052,"version":"4.0.1"},"reference-count":30,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CHDI Foundation grant","award":["P51 OD011092"],"award-info":[{"award-number":["P51 OD011092"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Huntington\u2019s disease (HD) arises from expanded CAG repeats in exon 1 of the Huntingtin (HTT) gene. The resultant misfolded HTT protein accumulates within neuronal cells, negatively impacting their function and survival. Ultimately, HTT accumulation results in cell death, causing the development of HD. A nonhuman primate (NHP) HD model would provide important insight into disease development and the generation of novel therapies due to their genetic and physiological similarity to humans. For this purpose, we tested CRISPR\/Cas9 and a single-stranded DNA (ssDNA) containing expanded CAG repeats in introducing an expanded CAG repeat into the HTT gene in rhesus macaque embryos. Analyses were conducted on arrested embryos and trophectoderm (TE) cells biopsied from blastocysts to assess the insertion of the ssDNA into the HTT gene. Genotyping results demonstrated that 15% of the embryos carried an expanded CAG repeat. The integration of an expanded CAG repeat region was successfully identified in five blastocysts, which were cryopreserved for NHP HD animal production. Some off-target events were observed in biopsies from the cryopreserved blastocysts. NHP embryos were successfully produced, which will help to establish an NHP HD model and, ultimately, may serve as a vital tool for better understanding HD\u2019s pathology and developing novel treatments.<\/jats:p>","DOI":"10.3390\/cells13100829","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T03:35:55Z","timestamp":1715744155000},"page":"829","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Generation of Rhesus Macaque Embryos with Expanded CAG Trinucleotide Repeats in the Huntingtin Gene"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8064-5762","authenticated-orcid":false,"given":"Junghyun","family":"Ryu","sequence":"first","affiliation":[{"name":"Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Statz","sequence":"additional","affiliation":[{"name":"Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1444-6575","authenticated-orcid":false,"given":"William","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiana","family":"Oyama","sequence":"additional","affiliation":[{"name":"Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Custer","sequence":"additional","affiliation":[{"name":"Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wienisch","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Chen","sequence":"additional","affiliation":[{"name":"CHDI Foundation, Princeton, NJ 08540, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2790-3555","authenticated-orcid":false,"given":"Carol B.","family":"Hanna","sequence":"additional","affiliation":[{"name":"Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA"},{"name":"Assisted Reproductive Technologies Core, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6760-3733","authenticated-orcid":false,"given":"Jon D.","family":"Hennebold","sequence":"additional","affiliation":[{"name":"Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA"},{"name":"Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1002\/mds.29228","article-title":"Prevalence and Incidence of Huntington\u2019s Disease: An Updated Systematic Review and Meta-Analysis","volume":"37","author":"Medina","year":"2022","journal-title":"Mov. 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