CpG Free Plasmids For Enhanced Duration & Reduced Toxicity Of Non-Viral Airway Gene Transfer.

Hyde SC

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European Society of Gene and Cell Therapy Conference, Bruges, 2008

The UK Cystic Fibrosis Gene Therapy Consortium is the combined research programme of the three UK gene therapy research groups that have performed cystic fibrosis gene transfer clinical studies. In support of our next phase of clinical studies we have undertaken an extensive pre-clinical research programme to identify a non-viral gene transfer formulation that:-

  1. Directs efficient pulmonary transgene expression after delivered by clinically relevant aerosolisation devices
  2. Is repeatedly administrable without loss of efficacy
  3. Is minimally inflammatory / toxic
  4. Is readily manufactured under cGMP.

During this evaluation we identified plasmid derived CG dinucleotides as the major source of host inflammation in response to non-viral gene delivery to the lung and thus developed a range of CG dinucleotide free expression vectors that are capable of sustained lung transgene expression in the absence of host inflammation.