Development of Medicinal Products Based on Gene-Editing Technology: Regulatory Practices

Abstract

Somatic cell genome-editing systems are the most recent gene therapy technology to treat patients with monogenic hereditary cancer or HIV. Gene editing allows for changing or completely removing a defective gene with regularly interspaced short palindromic repeat (CRISPR), zinc-finger nuclease (ZFN), and transcription activator-like effector nuclease (TALEN) systems.The aim of the study was to analyse the existing international experience and regulatory requirements relating to the development of medicinal products based on genome editing of postnatal somatic cells.This article describes the mechanism of action of CRISPR, ZFN, and TALEN systems and compares their advantages and disadvantages. Regulatory and legislative authorities should take a special approach to the development, manufacture, and assessment of medicinal products based on genome editing, as well as to the ethical aspects of their use. Current requirements and recommendations for the development of medicinal products based on genome editing are mostly limited to the need to evaluate the risks of off-target effects and late-onset adverse events and the possibility to adapt clinical trial design to surrogate endpoints, exclude healthy volunteers and comparison groups, and select initial doses for clinical trials based on scientific data. Thus, a regulatory approach should also be developed for the marketing authorisation of medicinal products based on genome-editing systems.