{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:17:20Z","timestamp":1792513040809,"version":"4.5.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      ATTR amyloidosis is a disease caused by abnormal deposition of TTR (transthyretin) protein in tissues. ART001 is an\n                      <jats:italic>in vivo<\/jats:italic>\n                      gene therapy drug using lipid nanoparticle (LNP) to deliver mRNA encoding SpCas9 (\n                      <jats:italic>Streptococcus pyogenes<\/jats:italic>\n                      Cas9) and a single guide RNA (sgRNA) for knocking-out of the\n                      <jats:italic>TTR<\/jats:italic>\n                      gene in hepatocytes and reducing serum TTR levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In an investigator-initiated trial (IIT) of ART001 for 10 ATTR Amyloidosis patients, each patient was given one dose of ART001 which ranged from 0.05\u202fmg\/kg to 1.0\u202fmg\/kg. The aim was to evaluate ART001\u2019s safety, side effects, PK, PD, and efficacy based on circulating TTR protein levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At 0.7\u202fmg\/kg in 3 subjects and 1\u202fmg\/kg in 3 subjects, TTR protein reductions averaged 84 and 92% at 72\u202fweeks. No infusion-related reactions (IRRs), serious adverse events (SAEs) or serious adverse reactions (SARs) were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A single injection of ART001 achieved &amp;gt; 80% TTR knock-down at doses &amp;gt; 0.5\u202fmg\/kg and lasted for at least 72\u202fweeks without IRRs, SARs or SAEs. ART001 has the potential to be a safe, effective and permanent therapeutic option for ATTR Amyloidosis patients. (Funded by Accuredit Therapeutics).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      Trial registration: ChiCTR, ChiCTR2400081216. Registered 26\n                      <jats:sup>th<\/jats:sup>\n                      Feb, 2024 - retrospectively registered,\n                      <jats:ext-link>https:\/\/www.chictr.org.cn\/showprojEN.html?proj=210566<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1783921","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T04:42:11Z","timestamp":1776228131000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical safety and tolerability of in vivo gene editing drug ART001 for ATTR amyloidosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Yasi","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Neurology, The Fourth Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Huang","sequence":"additional","affiliation":[{"name":"Clinical Research, Accuredit Therapeutics","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Qiu","sequence":"additional","affiliation":[{"name":"Discovery and Preclinical Research, Accuredit Therapeutics","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suna","family":"Yang","sequence":"additional","affiliation":[{"name":"Clinical Research, Accuredit Therapeutics","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Tao","sequence":"additional","affiliation":[{"name":"Discovery and Preclinical Research, Accuredit Therapeutics","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Peking Union Medical College Hospital","place":["Beijing, China"]},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Fourth Affiliated Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.1016\/j.jacc.2015.09.075","article-title":"Diagnosis, prognosis, and therapy of\u202ftransthyretin amyloidosis","volume":"66","author":"Gertz","year":"2015","journal-title":"J Am Coll 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