{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:36:51Z","timestamp":1785537411345,"version":"3.56.0"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T00:00:00Z","timestamp":1658102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001352","name":"National University of Singapore","doi-asserted-by":"publisher","award":["NUHSRO\/2019\/076\/STARTUP\/02"],"award-info":[{"award-number":["NUHSRO\/2019\/076\/STARTUP\/02"]}],"id":[{"id":"10.13039\/501100001352","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pericles.pericles-gcp.literatumonline.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Acute Myeloid Leukaemia (AML) is the most common blood cancer in adults. Although 2 out of 3 AML patients go into total remission after chemotherapies and targeted therapies, the disease recurs in 60%\u201365% of younger adult patients within 3\u2009years after diagnosis with a dramatically decreased survival rate. Therapeutic oligonucleotides are promising treatments under development for AML as they can be designed to silence oncogenes with high specificity and flexibility. However, there are not many well validated approaches for safely and efficiently delivering oligonucleotide drugs. This issue could be resolved by utilizing a new generation of delivery vehicles such as extracellular vesicles (EVs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we harness red blood cell\u2010derived EVs (RBCEVs) and engineer them via exogenous drug loading and surface functionalization to develop an efficient drug delivery system for AML. Particularly, EVs are designed to target CD33, a common surface marker with elevated expression in AML cells via the conjugation of a CD33\u2010binding monoclonal antibody onto the EV surface.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The conjugation of RBCEVs with the CD33\u2010binding antibody significantly increases the uptake of RBCEVs by CD33\u2010positive AML cells, but not by CD33\u2010negative cells. We also load CD33\u2010targeting RBCEVs with antisense oligonucleotides (ASOs) targeting <jats:italic>FLT3\u2010ITD<\/jats:italic> or miR\u2010125b, 2 common oncogenes in AML, and demonstrate that the engineered\u00a0EVs improve leukaemia suppression in in vitro and in vivo models of AML.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Targeted RBCEVs represent an innovative, efficient, and versatile delivery platform for therapeutic ASOs and can expedite the clinical translation of oligonucleotide drugs for AML treatments by overcoming current obstacles in oligonucleotide delivery.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.13255","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T06:46:16Z","timestamp":1658213176000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["<scp>CD33<\/scp>\u2010targeting extracellular vesicles deliver antisense oligonucleotides against <scp>FLT3\u2010ITD<\/scp> and <scp>miR<\/scp>\u2010125b for specific treatment of acute myeloid leukaemia"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7906-7635","authenticated-orcid":false,"given":"Huan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Institute for Digital Medicine, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"},{"name":"Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"},{"name":"Department of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences City University of Hong Kong  Kowloon Hong Kong SAR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Migara Kavishka","family":"Jayasinghe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute for Digital Medicine, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"},{"name":"Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Yew Meng","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute for Digital Medicine, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"},{"name":"Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute for Digital Medicine, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"},{"name":"Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Pirisinu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences City University of Hong Kong  Kowloon Hong Kong SAR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waqas Muhammad","family":"Usman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences City University of Hong Kong  Kowloon Hong Kong SAR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thach Tuan","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute for Digital Medicine, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"},{"name":"Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kah Wai","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Physics &amp; Applied Physics, School of Physical &amp; Mathematical Sciences Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhan Van","family":"Tran","sequence":"additional","affiliation":[{"name":"Division of Physics &amp; Applied Physics, School of Physical &amp; Mathematical Sciences Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anskar Y. H.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital The University of Hong Kong  Pok Fu Lam Hong Kong SAR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Hematology and Shenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Second People's Hospital The First Affiliated Hospital of Shenzhen University, Shenzhen University School of Medicine  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology and Shenzhen Bone Marrow Transplantation Public Service Platform, Shenzhen Second People's Hospital The First Affiliated Hospital of Shenzhen University, Shenzhen University School of Medicine  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh Tu\u00e2n","family":"Phan","sequence":"additional","affiliation":[{"name":"Division of Physics &amp; Applied Physics, School of Physical &amp; Mathematical Sciences Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6077-1566","authenticated-orcid":false,"given":"Minh T. 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