Method of Enhancing Translation Ability and Stability of RNA Molecules, Treatments and Kits

Technology Overview

mRNAs hold great promise in research and gene therapy but face two major drawbacks, namely low translation levels due to competition with endogenous mRNAs and lack of stability due to rapid degradation upon entering cells.

m6Am is a modified base and is found in some mRNAs immediately after the m7G cap at the 5' end. The inventors have shown that the introduction of m6Am into the 5' UTR of transcripts dramatically increases their stability (2-3 fold), thereby allowing it to persist for a longer period of time in cells. It also raises translation levels by promoting translation initiation. This technology requires a single m6Am, which can be easily incorporated into mRNAs using specific polymerases or enzymatic reactions. This invention therefore, facilitates the production of large amounts of a desired protein using in vitro protein production systems.

Potential Applications

• Kits to enhance protein yields in in vitro (cell-free) protein synthesis reactions and in vivo
• Increased protein production for gene therapy applications
• Enhanced mRNA translation in disease states for the treatment of the diseases/conditions

Advantages

• Enhanced stability of the transcript along with higher translation levels resulting in high protein yields
• The m6Am modification can be readily incorporated into mRNAs.