UP researchers recognized by the Gilead Genesis Program

The Gilead Genesis Program recently recognized two research projects led by i3S scientists. “iCoV2PLUS” - coordinated by Alexandra Moreira, aims to improve the manufacturing process of RNA and DNA vaccines against the various variants of SARS-CoV-2, and “Duo-DIU”, led by José das Neves, intends to develop a new prophylactic medicine capable of protecting women simultaneously from unplanned pregnancy and HIV-1 infection.

Created in 2013 with the aim of encouraging research, the production and sharing of scientific knowledge and enabling initiatives that lead to the implementation of good practices in the monitoring of patients, the Gilead GÉNESE Program awarded this year six research projects and seven community intervention projects. The public award ceremony took place at the Salão Nobre of the Rectory of the University of Lisbon.

Alexandra Moreira, leader of the i3S research group “Gene Regulation” and Principal Investigator at the Abel Salazar Institute of Biomedical Sciences (ICBAS), stresses that the 33 thousand euros funding that the project “iCoV2PLUS – Increased Production Levels Universal Sequence in SARS- CoV-2 vaccines” won will allow the team to “do proof-of-concept experiments”. To that end, she added, “we are going to use a small sequence of non-coding nucleotides to increase RNA stability in RNA vaccines, and increase production of recombinant DNA vaccines, with great benefits for society”.

“There are more than 100 vaccines being developed against Covid-19 and more than 30 of these vaccines are RNA or DNA. But one of the main challenges in RNA vaccines is to make mRNA more stable and in DNA vaccines it is to improve the efficiency of its production”, explains Alexandra Moreira. “During the last few years, our team has been dedicated to studying iPLUS, a small genetic sequence that increases RNA stability and increases the production of recombinant proteins. We also established strategic industrial partnerships to show that iPLUS increases the production of a monoclonal antibody used in immunotherapy to treat cancer”, she underlines.

In this project, Alexandra Moreira points out, “we are going to apply iPLUS to improve the production of DNA and mRNA vaccines for Covid-19 with the aim of contributing to the end of the pandemic. We will provide proof of concept that iPLUS increases mRNA stability and increases Spike protein production in five viral variants: original (Wuhan-Hu-1), Indian (Delta), UK (Alpha), Manaus (Gamma) and South Africa (Beta)”. The final objective, says the researcher from i3S and ICBAS, “is to improve the manufacturing process of RNA and DNA vaccines against these five variants of the virus. The iCoV2PLUS will thus have a strong impact on society, because it can reduce production costs and benefit the population in general, and because it makes industrial processes more efficient in accordance with good environmental practices and reduces the carbon footprint”.

At the beginning of the pandemic, Alexandra Moreira also points out, “we were actively involved in the i3S task force to carry out PCR tests, in collaboration with Hospitals and Health Centers. apply our knowledge to advance RNA and DNA vaccine technology for multiple variants of SARS-CoV-2”. The Gilead Génese Program, she adds, “is fundamental to the success of our project, because it will allow us to buy expensive reagents and carry out proof-of-concept experiments that we wouldn’t be able to do otherwise. At the same time, it will allow us to translate our scientific knowledge to the mRNA and DNA vaccine industries, benefiting society in general.”

A new two-drug IUD to protect women

As for the Duo-DIU project, which was awarded 35 thousand euros by the Gilead Genesis Program, it is led by José das Neves, a researcher in the group “Nanomedicines & Translational Drug Delivery”, and “intends to develop a new prophylactic drug capable of protecting women, simultaneously, of unplanned pregnancy and HIV-1 infection”.

These situations, stresses the researcher, constitute “two of the biggest concerns of women in terms of sexuality and health”. However, explains José das Neves, “the development of this medicine is not easy. Despite being highly effective as contraceptives, the intrauterine devices (commonly known by the acronym IUD) of a hormonal nature available on the market are based on technologies that only allow the delivery of drugs directly into the uterus and, in relation to HIV-1 infection, it is believed that some antiretroviral drugs are effective in protecting women against sexual transmission of the virus, but only when administered directly into the vagina”.

Thus, the objective of this project is “to develop a new IUD, called Duo-DIU, which contains two drugs: a contraceptive hormone (levonorgestrel) and an antiretroviral (dapivirine). The great innovation is related to its design that allows the drugs to be released simultaneously and only in the anatomical place where they are needed. Thus, levonorgestrel is released in the uterus (as is typical with hormonal IUDs), while dapivirine is released in the vagina. The controlled release of dapivirine in the vagina is based on a new advanced technology that involves the use of very small drug crystals (nanocrystals)”.

Duo-DIU, continues José das Neves, will be evaluated in the laboratory for its ability to release the two drugs in a prolonged way (over at least one year): “The differential release of levonorgestrel in the uterus and of dapivirine in the vagina will be measured through the use of an artificial device that simulates, in a laboratory environment, the uterine and vaginal spaces”.

The project will last two years and it is expected that the results obtained will support the realization of the first clinical trials. The Duo-DIU is intended to be a convenient (only single placement with annual replacement), safe and effective method of protecting women from unplanned pregnancy and HIV-1 infection.

In addition to the importance that the monetary award represents for the execution of this particular project, José das Neves stressed that “it is another public recognition of the excellence of the work that we have been developing at i3S in the area of preventing HIV/AIDS infection”.