2026-10-12T18:54:53Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33971422 2026-09-23T06:24:29Z category_19 portal_316 item_type_3 month_year_09_2026

Supplementary file 1_Functional-genomic prioritization identifies MED12 as a candidate RNAi vulnerability in acute myeloid leukemia: evaluation of a T22 peptide-functionalized LNP-siRNA formulation.docx Zhouchun Chen (25094836) Tianran Chai (25094839) Meichen Liu (8168148) Haigang Wu (1714363) Yangjie Li (5740295) Wenyuan Yang (5592968) Pharmacology acute myeloid leukemia CXCR4 functional genomics lipid nanoparticles MED12 RNA interference siRNA T22 peptide Background<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.</p>Methods<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.</p>Results<p>MED12 ranked highest in the integrated functional-genomic prioritization framework. In OCI-AML3 and THP-1 cells, TLNP-siMED12 produced replicated reductions in MED12 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&E images provided limited tolerability information.</p>Conclusion<p>Integrated functional-genomic prioritization identified MED12 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 in vivo target engagement remain to be established.</p> 2026-09-23T06:24:29Z Dataset Dataset 10.3389/fphar.2026.1923515.s001 https://figshare.com/articles/dataset/Supplementary_file_1_Functional-genomic_prioritization_identifies_MED12_as_a_candidate_RNAi_vulnerability_in_acute_myeloid_leukemia_evaluation_of_a_T22_peptide-functionalized_LNP-siRNA_formulation_docx/33971422 CC BY 4.0