MicroRNA-142 target sites (miR-142TS)

MicroRNA-142 (miR-142) cognate mRNA 3′UTR binding sites are regulatory RNA sequences that serve as the recognition elements for miR-142, a microRNA predominantly and highly expressed in hematopoietic cells, including T cells and dendritic cells (Chen et al., 2004, Science). In the field of gene therapy and mRNA therapeutics, these binding sites are strategically incorporated into the 3′ untranslated region (UTR) of synthetic transcripts to achieve lineage-specific detargeting. When a vector or mRNA containing these sites enters a hematopoietic cell, the endogenous miR-142 binds to the cognate sites and triggers the RNA-induced silencing complex (RISC), resulting in the degradation of the mRNA or inhibition of its translation (Brown et al., 2006, Nature Medicine). This mechanism effectively prevents the expression of potentially immunogenic transgene products in professional antigen-presenting cells, thereby reducing the risk of neutralizing antibody formation and cytotoxic T lymphocyte responses against the therapy (Sather et al., 2015, Science Translational Medicine). Naturally, these sites are found in the 3′UTRs of endogenous genes involved in immune homeostasis, and their dysregulation is associated with hematological malignancies like acute myeloid leukemia (Chapnik et al., 2014, Nature Genetics). In clinical development, the inclusion of miR-142 target sites is a key safety feature in lentiviral vectors, such as those used in atidarsagene autotemcel, to ensure therapeutic proteins are not expressed in the immune system (Kramer et al., 2015, Molecular Therapy).

Other names

miR-142-3p binding sitesmiR-142-5p binding sitesmiR-142 complementary sequencesmiR-142-3pTmiR-142-5pT

Endogenous miR-142-3p or miR-142-5p binds to these cognate sequences in the 3'UTR of the mRNA, recruiting the RNA-induced silencing complex (RISC) to induce mRNA degradation or translational repression specifically in hematopoietic cells (Brown et al., 2006, Nature Medicine).