RNA Therapeutics:
As a member of the Center for RNA Therapeutics, we are housed inside the Houston Methodist Research Institute. The Kiss RNA Lab is committed to the translation of basic science discoveries to benefit human health. Shortly after the lab opened, we joined the Houston Methodist Research Insitute’s RNA Therapeutics program (now the Center for RNA Therapeutics) and began working on our first therapeutic candidate. We continue to work with the HMRI’s RNA Core to streamline and optimize their production processes and to develop cancer-targeting RNA therapeutics. Our lab has also been developing methods to increase the potency of RNA therapeutics. These include the design of both novel RNA constructs and novel RNA sequence elements that increase the functional lifespan and/or the translation potential of the RNA therapeutic within cells.
We currently have several RNA therapy projects underway.
Our first RNA therapy project use a circular RNA (circRNA) to counter genes driving oncogenic transformation and cell migration in an in vitro model of breast cancer. That work earned Dr. Kiss a Career Development Award titled “Construction of circular RNAs to block miRNA-driven oncogenic transformation” from The American Society for Gene and Cell Therapy. This project was the key starting point for all of the Kiss RNA lab’s circRNA projects.
For our second family of projects, we are applying our expertise and experience to design, develop, and evaluate second generation circRNA vaccines to target COVID-19, Tuberculosis, and Mpox (formerly called Monkeypox). We have partnered with collaborators around the country to test our vaccine candidates and to move their development forward. For our COVID-19 candidates, we are also testing a new and different structurally stabilized version of the SARS-CoV-2 spike protein as an attempt to increase vaccine efficacy. Our collaborators at the University of Montana’s Vaccine Research Center are currently testing the effectiveness of our COVID-19 candidates in pre-clinical animal models. Also in collaboration with the University of Montana both our TB and Mpox vaccine candidates efforts are supported by a subcontract from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
Another circRNA project is a collaboration with Dr. Michelle Hastings at the University of Michigan. For this project we are testing whether a circRNA encoding Battenin protein can be a possible gene replacement therapy treatment for Batten’s Disease. Our early preliminary results have been promising in vitro and Dr. Hasting’s team have begun experiments in an animal model.
During our work, we evaluated nearly every known method to make circRNAs and noticed that most circRNA manufacturing methods were inefficient. Because of these defects in prior circRNA manufacturing techniques, we developed a novel technology to make circRNAs in vitro. We continue to optimize this technology and have filed a patent application to continue advancing our new technology towards the clinic. In addition to our vaccine projects, we plan to advance new circRNAs targeting different cancers, vaccines, and other genetic diseases.
Finally, the lab has also been developing novel mRNA therapy candidates to target glioblastoma multiforme tumor cells. What began as an attempt to use mRNAs to oppose the effects of a key transcription factor that drives the proliferation and metastasis of a subset of glioblastoma tumors has morphed into an exciting project that may have uncovered a new mechanism by which RNA drugs can function.
Current Support:
The Cancer Prevention Institute of Texas (1/2021 – 12/2025; RP200619; PI: Cooke, JP)
Houston Methodist Research Institute Career Cornerstone Award – (1/2021 – 12/2025; PI: Kiss, DL)
Houston Methodist Foundation – RNA Therapeutics Fund – (4/2022 – 12/2023; PI: Kiss, DL)
NIH- NIAID Contract #: 75N93019C00045-P00012-9999-3, subcontract #: PG23-61290-02 (TB vaccine, 8/2022-7/2024; PI: Evans)
NIH- NIAID Contract #: 75N93019C00045-P00012-9999-3, subcontract #: PG23-61299-02 (Mpox vaccine, 9/2022-9/2024; PI: Evans)
Past Support:
Houston Methodist Research Institute COVID-19 RNA Vaccine grant (4/2020 – 12/2021; PI: Kiss, DL)
Career Development Award from The American Society for Gene and Cell Therapy (12/2019 – 11/2020; PI: Kiss, DL)
The Cancer Prevention Institute of Texas (3/2018 – 12/2020; RP150611; PI: Cooke, JP)
