{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:11:27Z","timestamp":1790143887435,"version":"4.0.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute myeloid leukemia (AML) depends in part on transcriptional and epigenetic programs that can be difficult to target with conventional small molecules. RNA interference provides a potential approach to perturb such vulnerabilities, but target selection and intracellular siRNA delivery remain major challenges.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Public dependency datasets and primary AML and normal hematopoietic expression resources were integrated to prioritize candidate RNAi vulnerabilities. A T22 peptide-functionalized lipid nanoparticle (TLNP) formulation carrying siMED12 was evaluated in OCI-AML3 cells, with RT-qPCR and CCK-8 validation in THP-1 cells. A systemic OCI-AML3 mouse model was used for exploratory assessment of survival and tolerability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>MED12<\/jats:italic>\n                      ranked highest in the integrated functional-genomic prioritization framework. In OCI-AML3 and THP-1 cells, TLNP-siMED12 produced replicated reductions in\n                      <jats:italic>MED12<\/jats:italic>\n                      transcript abundance and cell viability across three independently initiated experiments. In OCI-AML3 cells, cellular uptake, free T22 competition, immunoblotting, apoptosis, migration and whole-well crystal violet-stained colony-like focus observations were each obtained once and are reported descriptively. In the systemic model, TLNP-siMED12 treatment was associated with prolonged survival; body weight, endpoint blood measurements and illustrative H&amp;amp;E images provided limited tolerability information.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Integrated functional-genomic prioritization identified\n                      <jats:italic>MED12<\/jats:italic>\n                      as a candidate RNAi vulnerability in AML. TLNP-siMED12 produced reproducible transcript and viability responses in the evaluated AML models and was associated with prolonged survival in the systemic OCI-AML3 model. Hematopoietic selectivity, receptor-dependent delivery and\n                      <jats:italic>in vivo<\/jats:italic>\n                      target engagement remain to be established.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1923515","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:49:47Z","timestamp":1790142587000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional-genomic prioritization identifies MED12 as a candidate RNAi vulnerability in acute myeloid leukemia: evaluation of a T22 peptide-functionalized LNP-siRNA formulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhouchun","family":"Chen","sequence":"first","affiliation":[{"name":"School of Medicine, Xinjiang University of Science and Technology","place":["Korla, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianran","family":"Chai","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Henan University","place":["Kaifeng, Henan, China"]},{"name":"Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center","place":["Goyang, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meichen","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Science, Henan University","place":["Kaifeng, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haigang","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Henan University","place":["Kaifeng, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangjie","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, Xinjiang University of Science and Technology","place":["Korla, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Henan University","place":["Kaifeng, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.jconrel.2024.02.018","article-title":"Lipopolymer mediated siRNA delivery targeting aberrant oncogenes for effective therapy of myeloid leukemia in preclinical animal models","volume":"367","author":"Ansari","year":"2024","journal-title":"J. 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