Preclinical Safety Evaluation Strategies of Gene Transfer Products: Regulatory and Technical Considerations

摘要

Abstract. Preclinical safety evaluation of gene transfer compounds is based on the strategy used for most new drugs and additionally includes certain aspects specific to biotechnology-derived products. Gene transfer compounds are most often composed of two entities: genetic material encoding a therapeutic protein, and a so-called vector, viral or non-viral, intended to deliver the gene into the target cell or tissue. Safety assessment of gene transfer products therefore tends to be more complicated than for more conventional drugs and other biotechnology-derived compounds. Some regulatory agencies have issued guidelines or points to consider for the preclinical and clinical evaluation of these products. However, the preclinical strategy must be developed on a case by case basis, according to the nature and pharmacological properties of the compounds to be tested. Special attention has to be paid to the choice of a relevant animal species as well as focusing on subsequent biodistribution, in order to evaluate any possible germinal transmission of the gene transfer products.Investigators have to cope with challenging analytical techniques for each compound such as quantitative polymerase chain reaction (PCR) analysis and assays to evaluate specific cell-mediated or humoral immune responses. Moreover, as gene transfer products are genetically modified organisms, specific confinement rules have to be applied for the handling of both products and treated animals. These rules are driven by national authorities and can differ from one country to another.