What is considered Good Practice on the assessment of GMO aspects for in-vivo gene therapy products?

A recent document released by the European Commission (EC) outlines Good Practice considerations when assessing genetically modified organism (GMO) related aspects, during the conduct of clinical trials with Adeno-associated virus (AAV) vectors.

AAV vectors are derived from a single stranded DNA virus, and can be used to produce genetically modified medicinal products.

While there are a number of manufacturing strategies that can be used to produce AAV clinical vectors, the basic elements are:

  •  The AAV ITR’s flanking the ‘gene of interest’ (this construct contains the cis elements necessary for packaging and replication of the single stranded DNA genome).
  • Genetic sequences (Rep and Cap) necessary for AAV replication and viral capsid proteins (generally provided in trans within a plasmid, baculoviral vector, or in a packaging cell line).
  • Helper virus functions: several approaches are possible, from the earlier approach of coinfection of the helper virus, to co-transfection with a plasmid or co-transduction with baculovirus derived vectors encoding the helper genes.
  • A cell line capable of supporting helper virus and AAV replication.

This European Research Area Progress Report (ERA) describes the potential hazards to human health, animals and the environment, associated with the use of AAVs, during and after clinical trials.

Risk management strategies used to minimise the likelihood of accidental exposure of health care professionals at the clinical trial site, should be listed in Section 3.6 of the common application form.

As long as the control measures described on the application form are implemented, the overall risk to human health and the environment should be negligible.

Access the ERA here.