Use of polyadenosine tail mimetics to enhance mRNA expression from genes associated with haploinsufficiency disorders.

ABSTRACT: Polyadenosine (poly(A)) tails are nearly ubiquitous in human messenger RNA (mRNA) governing mRNA stability and translation. Crucially, the poly(A) tail regulates cytoplasmic gene expression by undergoing controlled removal upon exposure to the cytoplasm. Upon removal, mRNA ceases protein production and may subsequently be degraded or silenced. We have generated a therapeutic modality that tethers a poly(A) tail mimetic on the 3' end of specifically targeted mRNAs, thereby enhancing their expression beyond their normal utility. This technology, which we term mRNA boosters, lends itself to uses on haploinsufficiency disorders, where reduced gene expression manifests in a disease state. By polyadenylating short RNA sequences antisense to the 3' untranslated region (UTR) of specific mRNAs, we

SUBMITTER: Torkzaban B 

PROVIDER: S-EPMC11834087 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature