Small Molecules That Target the RNAs That Cause Pulmonary Fibrosis and Polycystic Kidney Disease

Abstract

miRNAs are small, non-coding RNAs that are 20-23 nucleotides long and control gene expression by binding to the 3' untranslated region (UTR) of complementary mRNAs, causing degradation or translational repression. miRNAs control essential cellular processes, and their mutation and aberrant expression are associated with and causative of disease. Removal of overexpressed, disease-causing miRNAs is thus a viable therapeutic strategy. Here, our overall objective was to develop small molecules that target miR-21, which has been reported to cause pulmonary fibrosis. Small molecules were designed using the Disney lab identification strategy dubbed Inforna. Compounds that selectively degrade miR-21 were identified. LNAs targeting miRNA-21or miR-21 targeting small molecules were not found to inhibit lung myofibroblast differentiation or function in cellular models.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2023
Accession Number
AD1223433

Entities

People

  • Luke L. Lairson
  • Matthew D Disney

Organizations

  • Scripps Research

Tags

Fields of Study

  • Biology

Readers

  • Gulf War Illness and Chronic Multisymptom Illness in Veterans.
  • Molecular Genetics
  • Molecular and Cellular Biology