Dr Takis Athanasopoulos

School of Applied SciencesDr Takis Athanasopoulos

Dr Takis Athanasopoulos is currently (2013) a Lecturer in Molecular Biotechnology at the Faculty of Science and Engineering, University of Wolverhampton (UoW), UK (http://www.wlv.ac.uk/) and Academic Visitor & Research Consultant at the School of Biological Sciences, Royal Holloway University of London (RHUL), UK (http://www.rhul.ac.uk/).

Development of advanced vector systems for tailored/specific gene therapy and genetic vaccine applications

Introduction:

In gene therapy, DNA (or RNA!) that encodes for a therapeutic protein is packaged within a "vector", which is used to get the nucleic acid inside cells within the body. Once inside, the genetic information becomes expressed by the cell machinery, resulting in the production of therapeutic protein, which in turn treats the patient's disease. Two major classes of methods for gene delivery are those that use recombinant viruses (sometimes called biological nano-particles or viral vectors) and those that use naked DNA or DNA complexes (non-viral methods). Factors required for successful gene therapy/genetic vaccination thus include 1) successful uptake of vector by appropriate cells surface receptors/co-receptors (tissue specificity) 2) (DNA) vector entry into nucleus and expression 3) Evasion (or co-stimulation if a vaccine) of the host immune defenses. Optimization of such vector systems for gene/mRNA delivery toward tailored tissue/species-specific cell targets linked with immune-modulation as a specific design component is thus a prerequisite for successful gene therapy/vaccine applications.

Specific research questions and relevant methodology are therefore dependent upon multitude (and co-ordination of various design steps within the process) factors which we wish to consider in this project. The applicant wishes to develop as part of a national/international collaborative network (with colleagues both internally and external to the University) a cohort of tools tailored as useful molecular medicine (viral and non viral) vector systems toward gene therapy and genetic vaccine applications. These vector systems can be further tested/ applied in a battery of tests through collaborative links, with the ultimate aim to develop/generate a cohort of advanced molecular tools against a range of disorders (neuromuscular i.e DMD, cardiovascular, cancer- particularly focused on brain/renal tumour research-and diabetes). The applicant as part of the ERAS scheme will seek to form cross-school and intradepartmental initiatives/collaborative networks through project work with colleagues from the UoW. Additionally, a diverse range of projects are under development through external national/international collaborations and the ERAS scheme provided with the necessary seed funds to further develop, progress and complete a number of pilot studies. A number of intended outcomes as set milestones derived from this project (publications/grant funding/bid applications) are described below.

Aims/Objectives:

  1. Publications:  At least 3 high quality research papers as a co-author in the fields of gene therapy and/or genetic vaccines
  2. Grant Funding: At least 2 major grant applications to be submitted as bids towards external research funding/income generation as applicant (PI) or co-applicant (co-PI)
  3. At least 1 application to be submitted toward specialised research training/ travel fellowship conference participation


Methods:
State of the art methodology in the fields of gene therapy and/or genetic vaccination was applied, as appropriate. 
       
Research Design/Summary Findings and Future Work:
A range of advanced vector systems for tailor specific gene therapy and genetic vaccine applications has been introduced as part of the ERAS project and is under current development. The vector systems can be of non viral (Plasmids, Nanoparticles, Homing Endonuclease/Recombinases, CRISP-Rs) or viral origin (rAAV, rAdeno and rLenti systems). Nevertheless, the development and applications (in vitro and in vivo preclinical and toxicological studies, clinical PhaseI-IV/marketing etc) of such vector systems as a modern pharmaceutical product is a complex and time consuming exercise (5-10 years/product).

It is of note also that success in the field, may require multiple contributing forces (investigators, patient advocates, funding & regulatory bodies etc).  Applications of such advanced vector systems vary but can be potentially applied to a range of preclinical models of human disease and clinical settings under a unified umbrella. As part of this ERAS project a number of research networks have been attempted to be developed/established targeting disorders as diverse as DMD, Cancer/Brain tumours, HIV/AIDS, Cardiovascular but also various other Genetic Rare Diseases. Common parameters of such systems to be considered can be vector/cassette optimisation, safety and efficacy. The scope for future work beyond the duration of the ERAS scheme will be to develop and establish a strong national and international scientific network of contacts/colleagues which will allow further income generation through proposal bids and consultancy activities and appropriate research dissemination through publications/of high quality /impact studies which aim to directly contribute to the 2014 and future Research Excellence Frameworks (REFs) and will contribute to raise the International profile of the Faculty of Science and Engineering, the University of Wolverhampton and other collaborative Institutions.’ The ultimate aim would be to be able to collaboratively ameliorate a number of prevalent and devastating human genetic diseases.