Moreno Karlen, María Del Pilar

Research interests

My research work initially focused on the study of the evolution and genetic variability of RNA viruses. These viruses are characterised by high mutation rates, which generated that they circulate as a viral population, a set of closely genetically related viral variants. This makes RNA viruses highly adaptable, which represents one of the major obstacles to the prevention and control of diseases caused by these viruses. During this first stage of work, using the Hepatitis C virus as a model, we have contributed to the knowledge of the genetic variability of this virus, we have studied its recombination capacity, as well as the dynamics of viral populations. More recently, we have focused our work on understanding whether the composition of viral populations can affect the translational efficiency of this virus. In this way, I have contributed to the characterisation and understanding of these processes in order to generate relevant information that can be used when designing new antiviral strategies that take into account the high mutability and adaptability of these viruses.

On the other hand, the emergence and rapid spread of the SARS-CoV-2 virus highlighted the threat to human health posed by emerging viruses, for which no effective antiviral treatments or vaccines are available. At that time, our research team worked actively to overcome the various bottlenecks that our country faced during the course of the COVID-19 pandemic. In this regard, we developed the ‘COVID-19 RT-PCR Real TM Fast’ kit, a real-time RT-PCR test for the detection of SARS-CoV-2 virus, with which 40% of the national tests were performed in 2020. In addition, our group successfully transferred this methodology to more than 9 diagnostic centres, including public hospitals in Montevideo, as well as to laboratories of the University of the Republic located in the interior of the country and the INIA in Tacuarembó, creating a ‘Public Network of COVID-19 Laboratories’. We worked on validating the swabs designed by the Faculty of Chemistry for sampling and standardised a methodology that allowed us to study the presence of SARS CoV2 in wastewater as a tool to monitor the pandemic. We also conducted genomic surveillance of SARS CoV2 for more than two years and reported periodically to the Ministry of Public Health.

Given the experience generated and accumulated both in methodological aspects and in the training of young human resources, we are currently using all the methodological tools developed in the context of this pandemic, both molecular detection strategies and genomic surveillance strategies, to monitor the presence and spread of emerging and re-emerging viruses that are becoming more and more common in our region. In this sense, our work has focused on Dengue, Chikungunya, Zika, Mayaro, Western Equine Encephalitis and other viruses that may be of interest to our country. Also, considering the impact of mRNA vaccines in generating immunity against SARS CoV2 and the lack of effective vaccines for many of the aforementioned viruses, we are working on the development of an mRNA vaccine prototype for a virus of human interest such as the Mayaro arbovirus. In this line of research, we are fine-tuning this technology by modifying key characteristics that will allow it to increase its translation efficiency and stability and thus reduce its dose.

Finally, we are conducting a line of research involving the use of viral agents as cancer therapy. This line of research has allowed me to combine my previous studies, both at master's level and during my postdoctoral research stay at the Institut Pasteur in Montevideo on tumour processes, with my current virological training. Despite new advances in the knowledge of the molecular biology of cancer, classic treatments such as surgery, chemotherapy or radiotherapy continue to be the most widely used despite their high degree of resistance and/or harmful effect on the patient. It is in this context that the development of new therapeutic strategies that have a high lytic potential for malignant cells with little toxicity for normal cells has emerged. Within this new category are oncolytic viruses (OVs), viruses capable of mediating selective replication in tumour cells and lysing them both by mechanisms intrinsic to the virus and by induction of the anti-tumour immune system. In this line, we are currently working with two different viral models (picornaviridae and togaviridae) on the optimisation of the oncolytic potential of these viruses focused on the development of a new therapeutic strategy against lung adenocarcinoma and pancreatic cancer.

Working area

My work area lies at the intersection of molecular virology, applied immunology and biotechnology, with a particular focus on the study of RNA viruses and their impact on human health. I explore the genetic, evolutionary and functional dynamics of these viruses, seeking to understand the mechanisms underlying their high variability and adaptability, with the aim of generating knowledge that drives the development of innovative strategies in prevention, diagnosis and treatment.

This area also encompasses the design and optimisation of advanced technologies, such as mRNA vaccines and oncolytic viruses, integrating molecular biology, genomics and bioengineering tools to address complex problems in infectious diseases and cancer. It also includes genomic surveillance and health emergency response, with direct applications in public health and biomedicine.

In essence, work combines fundamental and translational research to contribute to the understanding of viruses and their therapeutic potential.