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Side effects of gene therapy vectors

Side effects of gene therapy vectors / Humanised system to test and certify safety of gene therapy modalities

Gene Therapy is the use of genetic information inside a therapeutic viral vector carrier that actively replaces and repairs “damaged” genes that cause disease or disability in a patient. GT is the most promising new, curative therapy for conditions like inherited disorders, some treatment resistant cancers and incurable viral infections like Hepatitis C or HIV.

The last 15 years have seen gene therapy graduate from an experimental, research approach to an approved treatment modality, with over 1800 gene therapy trials initiated or approved worldwide between 2015 and 2017. Especially 2017 has been a landmark year for gene therapy, with several licensed therapies now available to treat patients. Despite its recent success, there are still significant challenges. The target site to which a therapeutic viral vector delivers its payload into the genome of a patient can be missed with devastating consequences: the gene defect remains uncured and the “off-site” activity of the satellite gene can cause additional, sometimes fatal pathologies genotoxicity. Treatments for several genetic disorders are available including cancer, however, no standardised platform has been available to test safety, which is concerning following the development of leukaemia in several children treated for X-linked immunodeficiency by this therapy. A standardised test to determine and quantify the risk of genotoxicity for therapeutic viral vectors is of major need and importance.

Treatments for several genetic disorders are available including cancer, however, no standardised platform has been available to test safety, which is concerning following the development of leukaemia in several children treated for X-linked immunodeficiency using GT vectors.

Our project developed a screening platform that focuses on screening the safety of gene therapy vectors. From this work a spin out company Testavec Ltd has been set up which is developing the first standardised and validated testing framework and technology to certify safety of gene therapy modalities. Since 2015 over 1800 gene therapy (GT) trials were initiated or approved worldwide. Licensed products include “Glybera” (Uniqure), “Kymriah” (Novartis) and “Strimvelis” (GSK) have now entered the market.

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Testavec is developing a standardised, clinically validated and CE marked gene therapy therapeutic viral vector safety assay, based on sequential viral infection in an induced Pluripotent Stem Cell (iPSc) platform to scan and read-out gene expression of genes targeted by therapeutic viral vector integration.

The test platform is designed to:

  • certify gene therapy therapeutic viral vector safety in advance of use in clinical trials of novel “genotoxicity”, and
  • assess tolerance of gene therapy therapeutic viral vector in individual patients.

The aim of the Testavec genotox platform is to become the mandated certification process of the regulatory bodies as at present such a safety predicate does not exist for this new class of therapeutics.

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Meet the Principal Investigator(s) for the project

Dr Michael Themis - Dr Themis is a Reader in the Department of Life Sciences Brunel University London and an Honorary Lecturer at Imperial College, London. His research at Brunel concerns gene therapy efficacy and safety. Founding Director of TestaVec Ltd - A brunel University spin-out company Between 2015 and 2017 over 1800 gene therapy (GT) trials were initiated or approved worldwide. Large pharmaceutical companies including GSK, Novartis, Astra Zeneca and Pfizer are investing heavily in gene therapy virus technology and two new licensed products, ‘Glybera” (Uniqure) and Strimvelis (GSK) have now entered the market. Treatments for several genetic disorders are available including cancer, however, no standardised platform has been available to test safety, which is concerning following the development of leukaemia in several children treated for X-linked immunodeficiency by this therapy. Dr Themis has recently launched the first company that focusses on screening the safety of gene therapy. The technology developed and led by Dr Themis in collaboration with UCL, KCL, GeneWerk, Germany, the National Institute for Biological Standards and Control and NMI, Germany, won the SBRI InMutaGene CRACK-IT Challenge. This work, which was funded by the NC3Rs and sponsored by GSK and Novartis has generated the first human induced pluripotent stem cell (iPSc) based platform that evaluates the safety of gene therapy products. The intension is to use this technology prior to patient exposure as a pre-screening service that identifies patient tolerance to gene therapy and to profile vector side effects next to established reference standards. With IP filed, TestaVec Ltd, which is a spin-out of Brunel University will support academics and industry alike to enter their products safety into the clinic. Qualifications: BSc: 1st class honours with Brunel University London and University Prize PhD: 1994 entitled “Insertional mutagenesis:experiences at the hprt locus” Post Graduate Certificate in Learning and Teaching in Higher Education (PGCert) Post Graduate Certificate in Intellectual Property Law (PGCert) Training Persuasion and Assertiveness - 2008 PgCert in Teaching - 2008 PgCert in Patent Law - 2010 Blackboard Learn - 2012 Biological Monitoring for Health and safety – HSE Buxton 2012 Introduction to the Principles and Practices of working at Containment Level 3 – HPA Porton Down 2013

Related Research Group(s)

Genome Engineering and Maintenance

Genome Engineering and Maintenance - Diverse research network focused on molecular, cellular, organismal and computational aspects of genome biology.


Project last modified 14/07/2021