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

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.