The PCR assay in the preclinical safety evaluation of nucleic acid medicines

The polymerase chain reaction (PCR) is a highly efficient gene amplificatio n procedure which is increasingly being applied to the safety assessment of nucleic acid (NA) medicines such as gene therapies and DNA vaccines. Although clinical experience is limited, a number of potential safety issue s exist with these new compounds including toxicity associated With the exp ression of encoded gene products, autoimmunity due to the induction of anti -DNA antibodies and insertional mutagenesis. PCR enables these questions to be addressed and provides data on mRNA expression, biodistribution and int egration. In this review the use of PCR methodologies in the preclinical safety evalu ation of NA medicines is discussed. particular consideration is given to th e issues surrounding the use of PCR in regulatory toxicology, including sen sitivity requirements, cross-contamination problems, tissue sampling proced ures and good laboratory practice (GLP) compliance. In addition, the use of a PCR-based assay to demonstrate the integration of DNA vector into host D NA is described. As the use of PCR in the development of NA medicines will undoubtedly incre ase over the next few years, it is important that pathologists and toxicolo gists familiarise themselves with the principles and applications of this t echnique.