RNAmpMax · Maximization of amplification of next-generation RNA replicon vaccines through synergistic molecular and formulation design
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2019-01-02 → 2021-01-01
- Финансиране от ЕС
- 183 455 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Самоусилващите се РНК ваксини се изследват чрез нови молекулярни дизайни и формули, които да помогнат на повече РНК да проникне в клетката. Това позволява намаляване на дозата и цената на ваксините, като ги прави по-достъпни за хората по целия свят.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Maximization of amplification of next-generation RNA replicon vaccines through synergistic molecular and formulation design
Ribonucleic acid (RNA) is a cutting-edge vaccine platform, and the speed and scalability of this strategy has been highlighted during the COVID-19 pandemic. It is possible to make a vaccine against any pathogen with a known protein target, and the currently approved RNA vaccines have remarkably efficacy (>94%). Self-amplifying RNA is a next-generation type of RNA, wherein the RNA is able to make copies of itself once it gets delivered into a host cell, which minimizes the required dose of RNA and therefore cost of the vaccine. However, like all RNA, saRNA is sensed by the cell, which can both help and hinder the immunogenicity of a vaccine. The objectives of this project were to develop new saRNA formulations that increase the amount of RNA that gets into a cell, and to use new molecular designs of RNA to limit the inhibitory cellular sensing of RNA. The findings from this project will enable more potent and efficacious RNA vaccines that increase the accessibility of vaccines for the global population.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
As a Maria Skłodowska-Curie Fellow, I aim to develop formulated next-generation RNA replicons that are designed to overcome the limiting initial type I interferon response that inhibits amplification and protein expression. RNA replicons are currently a cutting edge nucleic acid platform for delivery of vaccines and therapeutics, as they do not require penetration into the nucleus like plasmid DNA, but possess self-amplification properties that results in more efficient protein expression than messenger RNA. While pDNA and mRNA have have demonstrated excellent results with low doses when tested in mice doses must be scaled up by two orders of magnitude to mirror these effects in nonhuman primates. This disparity reflects a non-linear dose-response relationship, where increased doses are associated with triggering of an interferon cascade which restricts protein expression. Under the supervision of Prof. Robin Shattock, a world leader in translational vaccines and clinical trials at Imperial College London, I aim to overcome this translational barrier for RNA replicons by focusing on maximizing protein expression. I intend to engineer synergistic increases in the amplification of RNA replicons through a combination of molecular modifications designed to minimize interferon response and co-delivery with synthetic single-strand oligonucleotides known to inhibit the interferon pathway. These molecular adaptions will be paired with a novel delivery polymer that directly incorporates oligonucleotides into the RNA polyplex, thus ensuring co-localization: to be synthesized in collaboration with Prof. Molly Stevens, a world leader in polymeric biomaterials, during a secondment at the Karolinska Institutet. This project is the first demonstration of synergistic molecular and formulation design to address the non-linear dose-response relationship, and could impact scalability of RNA vaccines and therapeutics making them more affordable and available in Europe and worldwide.
Оригинален текст от CORDIS (на английски).
Участници
- IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE · LondonКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз