{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:12:35Z","timestamp":1792264355093,"version":"4.4.0"},"reference-count":62,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"636","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,3,16]]},"abstract":"<jats:p>\n                    Prime editing is a highly versatile CRISPR-based genome editing technology that works without DNA double-strand break formation. Despite rapid technological advances, in vivo application for the treatment of genetic diseases remains challenging. Here, we developed a size-reduced\n                    <jats:italic>Sp<\/jats:italic>\n                    Cas9 prime editor (PE) lacking the RNaseH domain (PE2\n                    <jats:sup>\n                      \u0394\n                      <jats:italic>RnH<\/jats:italic>\n                    <\/jats:sup>\n                    ) and an intein-split construct (PE2 p.1153) for adeno-associated virus\u2013mediated delivery into the liver. Editing efficiencies reached 15% at the\n                    <jats:italic>Dnmt1<\/jats:italic>\n                    locus and were further elevated to 58% by delivering unsplit PE2\n                    <jats:sup>\n                      \u0394\n                      <jats:italic>RnH<\/jats:italic>\n                    <\/jats:sup>\n                    via human adenoviral vector 5 (AdV). To provide proof of concept for correcting a genetic liver disease, we used the AdV approach for repairing the disease-causing\n                    <jats:italic>\n                      Pah\n                      <jats:sup>enu2<\/jats:sup>\n                    <\/jats:italic>\n                    mutation in a mouse model of phenylketonuria (PKU) via prime editing. Average correction efficiencies of 11.1% (up to 17.4%) in neonates led to therapeutic reduction of blood phenylalanine, without inducing detectable off-target mutations or prolonged liver inflammation. Although the current in vivo prime editing approach for PKU has limitations for clinical application due to the requirement of high vector doses (7 \u00d7 10\n                    <jats:sup>14<\/jats:sup>\n                    vg\/kg) and the induction of immune responses to the vector and the PE, further development of the technology may lead to curative therapies for PKU and other genetic liver diseases.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.abl9238","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T13:58:11Z","timestamp":1647439091000},"source":"Crossref","is-referenced-by-count":200,"title":["In vivo prime editing of a metabolic liver disease in mice"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8142-0629","authenticated-orcid":true,"given":"Desir\u00e9e","family":"B\u00f6ck","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zurich, 8057 Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7799-2413","authenticated-orcid":true,"given":"Tanja","family":"Rothgangl","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zurich, 8057 Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2823-3271","authenticated-orcid":true,"given":"Lukas","family":"Villiger","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zurich, 8057 Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5993-9985","authenticated-orcid":true,"given":"Lukas","family":"Schmidheini","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zurich, 8057 Z\u00fcrich, Switzerland."},{"name":"Institute of Molecular Health Sciences, ETH Z\u00fcrich, 8093 Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5693-461X","authenticated-orcid":true,"given":"Mai","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Institute of Molecular Health Sciences, ETH Z\u00fcrich, 8093 Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4051-8344","authenticated-orcid":true,"given":"Nicolas","family":"Mathis","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zurich, 8057 Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Ioannidi","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Zurich, 8057 Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Rimann","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children\u2019s Research Center, University Children\u2019s Hospital Zurich, 8032 Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5343-2013","authenticated-orcid":true,"given":"Hiu Man","family":"Grisch-Chan","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children\u2019s Research Center, University Children\u2019s Hospital Zurich, 8032 Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-534X","authenticated-orcid":true,"given":"Susanne","family":"Kreutzer","sequence":"additional","affiliation":[{"name":"Genome Engineering and Measurement Laboratory (GEML), ETH Z\u00fcrich, 8093 Z\u00fcrich, Switzerland."},{"name":"Functional Genomics 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