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

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Tác giả: Jonathan M Alexander, Jeff Coller, Wenqian Hu, Michele H Jacob, Dingchang Lin, Christian Lopez, Jingyao Ma, Hai-Quan Mao, Sophie Martin, Katharine R Maschhoff, Yongzhi Sun, Bahareh Torkzaban, Yining Zhu

Ngôn ngữ: eng

Ký hiệu phân loại: 636.0885 Animal husbandry

Thông tin xuất bản: United States : Molecular therapy. Nucleic acids , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 210019

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 demonstrate that we can selectively and significantly enhance mRNA expression both
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