{"id":641430,"date":"2023-04-25T15:05:37","date_gmt":"2023-04-25T20:05:37","guid":{"rendered":"https:\/\/news.sellorbuyhomefast.com\/index.php\/2023\/04\/25\/efficient-engineering-of-human-and-mouse-primary-cells-using-peptide-assisted-genome-editing\/"},"modified":"2023-04-25T15:05:37","modified_gmt":"2023-04-25T20:05:37","slug":"efficient-engineering-of-human-and-mouse-primary-cells-using-peptide-assisted-genome-editing","status":"publish","type":"post","link":"https:\/\/newsycanuse.com\/index.php\/2023\/04\/25\/efficient-engineering-of-human-and-mouse-primary-cells-using-peptide-assisted-genome-editing\/","title":{"rendered":"Efficient engineering of human and mouse primary cells using peptide-assisted genome editing"},"content":{"rendered":"<p>Science &#038; Nature <\/p>\n<div>\n<div id=\"data-availability-section\" data-title=\"Data availability\">\n<h2 id=\"data-availability\">Data availability<\/h2>\n<p>The accession numbers for the RNA-seq dataset in this study is <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE223805\">GSE223805<\/a>(ref. <sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 55\" title=\"Zhang, Z. et al. Efficient engineering of human and mouse primary cells using peptide-assisted genome editing. NCBI. \n                https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE223805\n                \n               (2023).\" href=\"http:\/\/www.nature.com\/articles\/s41587-023-01756-1#ref-CR55\" id=\"ref-link-section-d118014348e2583\">55<\/a><\/sup>). The GRCh38\/hg38 human reference genome is publicly available. 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G.A.B. acknowledges NIH\/NHLBI (R01-HL119479). R.M.K. acknowledges NIH (R01-GM138908). E.J.W. acknowledges support from the NIH (AI105343, AI082630, AI108545, AI155577, AI149680 and U19AI082630), funding from the Allen Institute for Immunology and the Parker Institute for Cancer Immunotherapy. Work in the Wherry lab is supported by the Parker Institute for Cancer Immunotherapy. S.L.B. acknowledges NIH\/NCI (R35-CA263922). J.S. acknowledges NIH\/NCI (R01-CA258904).<\/p>\n<\/div>\n<div id=\"author-information-section\" aria-labelledby=\"author-information\" data-title=\"Author information\">\n<h2 id=\"author-information\">Author information<\/h2>\n<div id=\"author-information-content\">\n<h3 id=\"affiliations\">Authors and Affiliations<\/h3>\n<ol>\n<li id=\"Aff1\">\n<p>Epigenetics Institute, University of Pennsylvania, Philadelphia, PA, USA<\/p>\n<p>Zhen Zhang,\u00a0Diqiu Ren,\u00a0Kunhua Qin,\u00a0Sierra M. Collins,\u00a0Hua Huang,\u00a0Chad A. Komar,\u00a0Peter F. Bailer,\u00a0Gerd A. Blobel,\u00a0Rahul M. Kohli,\u00a0Shelley L. Berger\u00a0&#038;\u00a0Junwei Shi<\/p>\n<\/li>\n<li id=\"Aff2\">\n<p>Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA<\/p>\n<p>Zhen Zhang,\u00a0Sierra M. Collins,\u00a0Hua Huang\u00a0&#038;\u00a0Shelley L. Berger<\/p>\n<\/li>\n<li id=\"Aff3\">\n<p>Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA<\/p>\n<p>Amy E. Baxter,\u00a0Zeyu Chen,\u00a0Hua Huang\u00a0&#038;\u00a0E. John Wherry<\/p>\n<\/li>\n<li id=\"Aff4\">\n<p>Institute for Immunology and Immune Health, University of Pennsylvania, Philadelphia, PA, USA<\/p>\n<p>Amy E. Baxter,\u00a0Zeyu Chen\u00a0&#038;\u00a0E. John Wherry<\/p>\n<\/li>\n<li id=\"Aff5\">\n<p>Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA, USA<\/p>\n<p>Diqiu Ren,\u00a0Chad A. Komar\u00a0&#038;\u00a0Junwei Shi<\/p>\n<\/li>\n<li id=\"Aff6\">\n<p>Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA<\/p>\n<p>Diqiu Ren,\u00a0Chad A. Komar\u00a0&#038;\u00a0Junwei Shi<\/p>\n<\/li>\n<li id=\"Aff7\">\n<p>Division of Hematology, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA<\/p>\n<p>Kunhua Qin\u00a0&#038;\u00a0Gerd A. Blobel<\/p>\n<\/li>\n<li id=\"Aff8\">\n<p>Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA<\/p>\n<p>Peter F. Bailer,\u00a0Jared B. Parker\u00a0&#038;\u00a0Rahul M. Kohli<\/p>\n<\/li>\n<li id=\"Aff9\">\n<p>Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA<\/p>\n<p>Peter F. Bailer\u00a0&#038;\u00a0Rahul M. Kohli<\/p>\n<\/li>\n<li id=\"Aff10\">\n<p>Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA<\/p>\n<p>E. John Wherry<\/p>\n<\/li>\n<\/ol>\n<h3 id=\"contributions\">Contributions<\/h3>\n<p>Z.Z., E.J.W., S.L.B. and J.S. conceived and developed the Peptide-Assisted Genome Editing (PAGE) approach and designed the research. Z.Z., A.E.B., D.R., K.Q., Z.C., S.M., H.H., C.A.K., P.F.B. and J.B.P. performed experiments and analyzed the data. G.A.B., R.M.K., E.J.W., S.L.B. and J.S. supervised the research. Z.Z. and J.S. drafted the manuscript. Z.Z., A.E.B., G.A.B., R.M.K., E.J.W., S.L.B. and J.S. reviewed and edited the manuscript with input from all authors. All authors read and approved the final manuscript.<\/p>\n<h3 id=\"corresponding-author\">Corresponding authors<\/h3>\n<p id=\"corresponding-author-list\">Correspondence to<br \/>\n                <a id=\"corresp-c1\" href=\"http:\/\/www.nature.com\/mailto:wh****@****************nn.edu\" data-original-string=\"eRVCJnRDEQL3zWjDV8BAXA==7f4O0OKqBAqrkDMqYU8TOzzxBQ0LxEcb8smxtb8cP6kwZ4=\" title=\"This contact has been encoded by Anti-Spam by CleanTalk. Click to decode. To finish the decoding make sure that JavaScript is enabled in your browser.\">E. John Wherry<\/a>, <a id=\"corresp-c2\" href=\"http:\/\/www.nature.com\/mailto:be*****@****************nn.edu\" data-original-string=\"IurqgciSxCHQtgzxi6bQFg==7f4tLXxAAF0Lfp70BVm0o8CtZjtS7wEPXxFJnf+mdKPXZ4=\" title=\"This contact has been encoded by Anti-Spam by CleanTalk. Click to decode. To finish the decoding make sure that JavaScript is enabled in your browser.\">Shelley L. Berger<\/a> or <a id=\"corresp-c3\" href=\"http:\/\/www.nature.com\/mailto:ju***@***nn.edu\" data-original-string=\"QTF5KpUVk4lm2wlVm+0z3w==7f4E+RX9hqeRMXoDORCx5+l9Q==\" title=\"This contact has been encoded by Anti-Spam by CleanTalk. Click to decode. To finish the decoding make sure that JavaScript is enabled in your browser.\">Junwei Shi<\/a>.<\/p>\n<\/div>\n<\/div>\n<div id=\"ethics-section\" data-title=\"Ethics declarations\">\n<h2 id=\"ethics\">Ethics declarations<\/h2>\n<div id=\"ethics-content\">\n<h3 id=\"FPar2\">Competing interests<\/h3>\n<p>Z.Z., A.E.B., Z.C., J.B.P., R.M.K., E.J.W., S.L.B. and J.S. through the University of Pennsylvania have filed a patent application on aspects of this work. E.J.W. is a member of the Parker Institute for Cancer Immunotherapy which supported this study. E.J.W. is an advisor for Danger Bio, Janssen, New Limit, Marengo, Pluto Immunotherapeutics Related Sciences, Santa Ana Bio, Synthekine and Surface Oncology. E.J.W. is a founder of and holds stock in Surface Oncology, Danger Bio and Arsenal Biosciences. R.M.K. is on the Scientific Advisory Board for Life Edit, Inc.<\/p>\n<\/p><\/div>\n<\/div>\n<div id=\"peer-review-section\" data-title=\"Peer review\">\n<h2 id=\"peer-review\">Peer review<\/h2>\n<div id=\"peer-review-content\">\n<h3 id=\"FPar1\">Peer review information<\/h3>\n<p><i>Nature Biotechnology<\/i> thanks Meisam Kararoudi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.<\/p>\n<\/p><\/div>\n<\/div>\n<div id=\"additional-information-section\" data-title=\"Additional information\">\n<h2 id=\"additional-information\">Additional information<\/h2>\n<p><b>Publisher\u2019s note<\/b> Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.<\/p>\n<\/div>\n<div id=\"Sec36-section\" data-title=\"Supplementary information\">\n<h2 id=\"Sec36\">Supplementary information<\/h2>\n<\/div>\n<div id=\"Sec37-section\" data-title=\"Source data\">\n<h2 id=\"Sec37\">Source 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0-.92-.08-1.33-.25-.41-.16-.77-.4-1.08-.7-.3-.31-.54-.69-.72-1.13-.17-.44-.26-.95-.26-1.52zm4.61-.62c0-.55-.11-.98-.34-1.28-.23-.31-.58-.47-1.06-.47-.41 0-.77.15-1.08.45-.31.29-.5.73-.57 1.3zm3.01 2.23c.31.24.61.43.92.57.3.13.63.2.98.2.38 0 .65-.08.83-.23s.27-.35.27-.6c0-.14-.05-.26-.13-.37-.08-.1-.2-.2-.34-.28-.14-.09-.29-.16-.47-.23l-.53-.22c-.23-.09-.46-.18-.69-.3-.23-.11-.44-.24-.62-.4s-.33-.35-.45-.55c-.12-.21-.18-.46-.18-.75 0-.61.23-1.1.68-1.49.44-.38 1.06-.57 1.83-.57.48 0 .91.08 1.29.25s.71.36.99.57l-.74.98c-.24-.17-.49-.32-.73-.42-.25-.11-.51-.16-.78-.16-.35 0-.6.07-.76.21-.17.15-.25.33-.25.54 0 .14.04.26.12.36s.18.18.31.26c.14.07.29.14.46.21l.54.19c.23.09.47.18.7.29s.44.24.64.4c.19.16.34.35.46.58.11.23.17.5.17.82 0 .3-.06.58-.17.83-.12.26-.29.48-.51.68-.23.19-.51.34-.84.45-.34.11-.72.17-1.15.17-.48 0-.95-.09-1.41-.27-.46-.19-.86-.41-1.2-.68z" fill="#535353"/></g></svg>\"><\/a><\/p>\n<div>\n<h3 id=\"citeas\">Cite this article<\/h3>\n<p>Zhang, Z., Baxter, A.E., Ren, D. <i>et al.<\/i> Efficient engineering of human and mouse primary cells using peptide-assisted genome editing.<br \/>\n                    <i>Nat Biotechnol<\/i>  (2023). https:\/\/doi.org\/10.1038\/s41587-023-01756-1<\/p>\n<p><a data-test=\"citation-link\" data-track=\"click\" data-track-action=\"download article citation\" data-track-label=\"link\" data-track-external rel=\"nofollow\" href=\"https:\/\/citation-needed.springer.com\/v2\/references\/10.1038\/s41587-023-01756-1?format=refman&#038;flavour=citation\">Download citation<\/a><\/p>\n<ul data-test=\"publication-history\">\n<li>\n<p>Received<span>: <\/span><span><time datetime=\"2022-08-03\">03 August 2022<\/time><\/span><\/p>\n<\/li>\n<li>\n<p>Accepted<span>: <\/span><span><time datetime=\"2023-03-22\">22 March 2023<\/time><\/span><\/p>\n<\/li>\n<li>\n<p>Published<span>: <\/span><span><time datetime=\"2023-04-24\">24 April 2023<\/time><\/span><\/p>\n<\/li>\n<li>\n<p><abbr title=\"Digital Object Identifier\">DOI<\/abbr><span>: <\/span><span>https:\/\/doi.org\/10.1038\/s41587-023-01756-1<\/span><\/p>\n<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div><\/div>\n<p><a href=\"https:\/\/www.nature.com\/articles\/s41587-023-01756-1\" class=\"button purchase\" rel=\"nofollow noopener\" target=\"_blank\">Read More<\/a><br \/>\n Zhen Zhang<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Data availabilityThe accession numbers for the RNA-seq dataset in this study is GSE223805(ref. 55). The GRCh38\/hg38 human reference genome is publicly available. Key plasmids, Cas9-T6N and Cas12a-T8N have been deposited at Addgene (plasmid ID, 199604\u2013199605). Source data are provided with this paper, including unprocessed Western blots.ReferencesDoudna, J. A. The promise and challenge of therapeutic genome<\/p>\n","protected":false},"author":1,"featured_media":641431,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[25304,30555,536],"tags":[],"class_list":{"0":"post-641430","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-efficient","8":"category-engineering","9":"category-science-nature"},"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/posts\/641430","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/comments?post=641430"}],"version-history":[{"count":0,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/posts\/641430\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/media\/641431"}],"wp:attachment":[{"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/media?parent=641430"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/categories?post=641430"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/tags?post=641430"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}