Gene Therapy and Pharmacogenomics - TerGenOMIC

Reference of the Group:

GIUV2021-519

 
Description of research activity:
The proposed research group is the formalisation of an existing group with a history of over 20 years attached to the Department of Pharmacology of the Faculty of Medicine but not registered on the University of Valencia Research Groups (GIUV) platform. The group's coordinator was the Professor of Pharmacology Mr. Salvador F. Aliño Pellicer, who has just joined the body of UV emeritus professors. This September, it was handed over to a new generation and Dr. María José Herrero, assistant professor and doctor of the same department, has taken on the leadership of the group. Throughout this period of time, the group has participated in the development of non-viral gene therapy since its beginnings. In this sense, numerous scientific contributions have been made in international specialised journals, reporting the progress made in the translational research process for gene therapy from studies in cell cultures to its application in large animals in vivo in such complex scenarios as liver transplantation and in human organs ex vivo. Optimised strategies for targeted entry of DNA (hAAT, hIL10 and other genes) into the liver have been developed in mice, rats, pigs and patient liver...The proposed research group is the formalisation of an existing group with a history of over 20 years attached to the Department of Pharmacology of the Faculty of Medicine but not registered on the University of Valencia Research Groups (GIUV) platform. The group's coordinator was the Professor of Pharmacology Mr. Salvador F. Aliño Pellicer, who has just joined the body of UV emeritus professors. This September, it was handed over to a new generation and Dr. María José Herrero, assistant professor and doctor of the same department, has taken on the leadership of the group. Throughout this period of time, the group has participated in the development of non-viral gene therapy since its beginnings. In this sense, numerous scientific contributions have been made in international specialised journals, reporting the progress made in the translational research process for gene therapy from studies in cell cultures to its application in large animals in vivo in such complex scenarios as liver transplantation and in human organs ex vivo. Optimised strategies for targeted entry of DNA (hAAT, hIL10 and other genes) into the liver have been developed in mice, rats, pigs and patient liver segments, and efficient expression of the genes has been achieved with a strategy well tolerated by animals. We are currently working on the delivery of the IL10 gene in liver transplantation in pigs with the aim of modulating the rejection immune response and in human intestinal segments affected by Crohn's disease or colitis to evaluate its potential efficacy in blocking the exacerbated inflammatory response (FIS project). Within the area of gene therapy, our laboratory has also been developing the production of gene and cellular vaccines with anti-tumor capacity. To do this, irradiated tumor cells are modified (to prevent them from reproducing) to stimulate the immune response against them. This is done in two ways: on the one hand, the cells have been modified by adding genes that promote immune activation (GM-CSF, IL12) and on the other, the cells are modified by silencing the genes capable of suppressing the immune system's response (Foxp3, CTLA4) and thus allow it to act more effectively (AVI project). Furthermore, for about 12 years, the group has also focused on research in the very recent field of pharmacogenomics. This field of research focuses on the study of genetic variants present in pharmacogens (those that encode proteins responsible for the absorption, transport, metabolism and elimination processes of drugs) to determine possible associations between these interindividual variants and the effect of certain drugs. These genetic variants, mainly SNPs (single nucleotide polymorphisms) are not pathological per se but they can affect the efficacy and toxicity of drugs and generate serious disorders in patients who present one or more of these variants. In our group, we work in this area with a global vision and, therefore, we offer clinical services of any specialty, such as transplants, cancer, inflammatory diseases, dermatology, etc., the possibility of performing pharmacogenetic testing. In this sense, we have developed several analysis panels based on Mass Array and PCR that allow us to analyse all the genetic variants with the most scientific evidence as well as others that need more information but may be of interest since they affect key genes. Our group has also published several specialised articles in this field and we are currently participating in several national research projects that aim to transfer the procedure to clinical practice (IMPACT).
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Web:
 
Scientific-technical goals:
  • Entregar de manera eficiente genes a los organos diana y que estos se expresen en niveles suficientes para ejercer un efecto terapeutico
  • Desarrollo de vacunas antitumorales capaces de frenar la respuesta de inmunotolerancia que el tumor induce para eludir al sistema inmunitario
  • Determinar las asociaciones geneticas que condicionan el efecto de los farmacos para poder personalizar la pauta terapeutica optima a cada paciente
 
Research lines:
  • Gene Therapy.Non-viral gene therapy: we study naked DNA gene delivery procedures in 'in vivo' animal models and 'ex vivo' human models for clinical translation, as well as developing immunotherapy-based anti-tumor gene vaccines by silencing immune checkpoints.
  • Pharmacogenomics.We study the association of genetic variants present in prorein-coding genes that interact with drugs in the body with the effects they cause in patients. With this we aim to improve pharmacological treatments and adapt them to each individual.
 
Group members:
Name Nature of participation Entity Description
MARÍA JOSÉ HERRERO CERVERADirectorUniversitat de València
Research team
LUIS SENDRA GISBERTMemberUniversitat de València
LUIS SENDRA GISBERTMemberDesconocidaDesconocido
SALVADOR FRANCISC ALIÑO PELLICERCollaboratorUniversitat de València
 
CNAE:
  • -
 
Associated structure:
  • Pharmacology
 
Keywords:
  • Terapia génica, no viral, PCR cuantitativa, DNA, RNA, vacunas antitumorales, delivery, silenciamiento
  • farmacogenética, farmacogenómica, genotipado, reacciones adversas, toxicidad