Novel Bacteriophage Vector

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Overview A team at Imperial College generated a new generation of hybrid prokaryotic-eukaryotic viral vector as a chimera between eukaryotic AAV and the filamentous M13 bacteriophage, named AAVP (AAV/phage), both contain single stranded DNA genome. They have introduced key modifications including changing charge distribution on phage surface and engineering it to target different tropisms to enable the hybrid to enter human cells and enable targeted systemic gene delivery and enhance long-term gene expression.   Technology This vector expresses three to five copies of the cyclic RGD4C (CDCRGDCFC) ligand on the phage pIII minor coat protein allowing systemic and specific targeting to the αvβ3-integrin receptor, which are expressed primarily on tumour vasculature and tumour cells, and are absent or expressed at low levels in normal endothelium and tissues. This technology has been tested as a gene therapy for glioblastoma as a first indication. Early preclinical data showing efficient and specific reporter gene transfer in vitro/cell culture and ex vivo tumour cell killing using HStk/ ganciclovirus. Besides gene therapy this technology shows promise in applications including phage display, vaccine development, bacterial detection systems and nanotechnology. Development stage Funding received from Brain Tumour Research Campaign and Children with Cancer UK has allowed the team to establish in vivo animal models, including intracranial tumours with luciferase-labelled human glioblastoma cells. Preliminary data shows tumour cell death enhanced in combination with temozolomide.   Intellectual property Intellectual property package consists of four patents and considerable know-how.