Targeted degradation of oncogenic BCR-ABL by silencing the gene of NEDD8 E3 ligase RAPSYN.

ABSTRACT: Tyrosine kinase inhibitors have been the standard treatment for patients with Philadelphia chromosome-positive (Ph⁺) leukemia. However, a series of issues, including drug resistance, relapse and intolerance, are still an unmet medical need. Here, we report the targeted siRNA-based lipid nanoparticles in Ph⁺ leukemic cell lines for gene therapy of Ph⁺ leukemia, which specifically targets a recently identified NEDD8 E3 ligase RAPSYN in Ph⁺ leukemic cells to disrupt the neddylation of oncogenic BCR-ABL. To achieve the specificity for Ph⁺ leukemia therapy, a single-chain fragment variable region (scFv) of anti-CD79B monoclonal antibody was covalently conjugated on the surface of OA2-siRAPSYN lipid nanoparticles to generate the targeted lip

SUBMITTER: Sun Y 

PROVIDER: S-EPMC11089668 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature