RNA-based antisense platform for the treatment of human diseases

­Background

The central dogma of molecular biology demonstrates the two steps of gene expression, DNA transcription and mRNA translation, which generate functional proteins for any living cells. In any disease state, phenotypic changes are driven by insufficient production of protective proteins or overproduction of pathogenic proteins made by translation machinery. RNA-based disease mechanisms and therapeutics have become an important emerging field based on the landmark development of mRNA vaccines against RNA viruses and antisense oligonucleotides (ASOs) for genetic disorders.

Technology Overview

Researchers at the University of Rochester have developed a generic method and platform to design novel translation-manipulating ASO compound to target novel target mRNAs for testing their therapeutical potential. We have discovered molecular mechanisms that control mRNA translation efficiency via upstream open reading frame (uORF), main open reading frame (mORF), and their surrounding double-stranded RNA structure. Based on these molecular mechanisms, we invented three types of ASO to modulate protein expression as a novel biotechnology toolbox and laid the foundation for therapeutic development.

Figure 1

Benefits

This platform offers the opportunity to develop novel RNA-based therapeutics for “undruggable” targets in cardiac hypertrophy and organ fibrosis, among other human diseases. This ASO system has shown success in animal heart failure disease models in the laboratory. These innovative translation-manipulating ASOs can be used to enhance the translation of protective and beneficial proteins, while also repressing the translation of the pathogenic and detrimental proteins in any disease conditions.

Applications

  • Heart diseases
  • Metabolic syndrome
  • Organ fibrosis (in lung, liver, kidney, heart, etc.)
  • Duchenne Muscular Dystrophy
  • Huntington’s disease
  • Brain cancer
  • Spinal muscular atrophy
  • Familial amyloid polyneuropathy
  • Familial chylomicronemia syndrome
  • Other rare genetic diseases.
URV Reference Number: 6-21092B
Patent Information:
Category(s):
Therapeutic
For Information, Contact:
Matan Rapoport
University of Rochester
585.276.6600
matan.rapoport@rochester.edu
Inventors:
Peng Yao
Omar Hedaya
Keywords: