Risk assessments of clinical applications involving genetically modified viral vectors are carried out according
to general principles that are implemented in many national and regional legislations, e.g., in Directive 2001/18/EC of the
European Union. Recent developments in vector design have a large impact on the concepts that underpin the risk assessments
of viral vectors that are used in clinical trials. The use of (conditionally) replication competent viral vectors
(RCVVs) may increase the likelihood of the exposure of the environment around the patient, compared to replication defective
viral vectors. Based on this assumption we have developed a methodology for the environmental risk assessment
of replication competent viral vectors, which is presented in this review. Furthermore, the increased likelihood of exposure
leads to a reevaluation of what would constitute a hazardous gene product in viral vector therapies, and a keen interest
in new developments in the inserts used. One of the trends is the use of inserts produced by synthetic biology. In this
review the implications of these developments for the environmental risk assessment of RCVVs are highlighted, with examples
from current clinical trials. The conclusion is drawn that RCVVs, notwithstanding their replication competency,
can be applied in an environmentally safe way, in particular if adequate built-in safeties are incorporated, like conditional
replication competency, as mitigating factors to reduce adverse environmental effects that could occur.
Environmental risk assessment, genetically modified organism, replication competent viral vector, potentially
hazardous gene product, bioinformatics.
National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands.