UTR optimization for translational control of mRNA therapeutics
Name of applicant
Bente Kring Hansen
Title
Postdoctoral Fellow
Institution
The Center for RNA Therapeutics in the Houston Methodist Research Institute (HMRI), Houston, Texas, USA
Amount
DKK 1,020,000
Year
2023
Type of grant
Internationalisation Fellowships
What?
We propose to engineer structural elements into the UTRs of messenger RNA (mRNA) that interact with proteins that are overexpressed in cancer cells to induce the translation of the exogenous therapeutic mRNA.
Why?
mRNA therapies are being explored for use in vaccines for viral and bacterial infections as well as personalized cancer vaccines, where the mRNA contains the code to produce an antigen to train the immune system against these diseases. Current mRNA therapies use UTRs from Beta-globin mRNA which are associated with accumulation of the antigens in unwanted cell-types and off-target effects. Therefore, with this project I aim to design and construct new mRNAs which allows for cell-specific delivery and translation of our therapeutic mRNA and reduces off-target effects.
How?
To achieve these goals, I will implement unique RNA motifs into the UTRs of mRNA that binds to cancer biomarkers such as human antigen R (HuR). Cell specific delivery and translation efficacy of these novel mRNA constructs will be evaluated by fluorescent-based reporter assays in cancer and primary cell lines.