TestAVec CSO, Professor Michael Themis, also Head of the Gene Therapy research group at Brunel University London, and his team have conducted ground-breaking research that goes some way to uncovering why lentiviral vectors similar to HIV, may have caused leukaemia in many of the children receiving gene therapy for “Bubble Boy disease” - a rare but fatal immune deficiency disorder that required babies to be kept inside a plastic bubble to protect them from infection; whilst the therapy initially cured the children, many went on to develop leukaemia.
The team (which included both TestAVec and Brunel researchers, long term collaborators GeneWerk GmbH, and scientists from Edinburgh and UCL Universities) published their compelling findings this week in Gene Therapy (published by Springer Nature) with the title ‘HIV- 1 lentivirus tethering to the genome is associated with transcription factor binding sites found in genes that favour virus survival’. The research shows that HIV-1 actually targets and binds to transcription factor binding sites essential for its own gene expression and survival to firmly tether itself to the host genome where it then resides permanently. Moreover, examination of the functional properties of genes chosen for vector integration suggests a preference for binding to those neighbouring genes previously associated with insertional mutagenesis and potential carcinogenesis.
The researchers utilised both human stem cells cultured as 3D spheroids and their differentiated mature human cellular counterparts as human surrogate tissues to perform their diagnostic research. TestAVec uses this novel system to perform bespoke safety diagnostics and a safety by design service for Gene Therapy Companies developing gene therapies to reduce the risk that adverse health effects will be seen during clinical trials.