Strategies for nonviral nanoparticle‐based delivery of CRISPR/Cas9 therapeutics

Abstract

CRISPR-based genome editing technology has become an important potential therapeutic tool for various diseases. A vital challenge is to reach a safe, efficient, and clinically suitable delivery of a CRISPR-associated protein and a single-guide RNA. A possible translational approach to applying CRISPR-based technology is the use of viral vectors such as adeno-associated virus. However, such vectors give long-term exposure in vivo that may increase potential off-target effects as well as the risk of immunogenicity. Therefore, limitations to clinical applications are addressed using nonviral delivery systems such as nanoparticle-based delivery strategies. Today, the nanoparticle-based delivery approach is becoming more and more attractive in gene therapeutics because of its specific targeting, scale-up efficiency, efficacy of customization, minor stimulation of immune response, and minimal exposure to nucleases. In this review, we will present the most recent advances in developing innovations and potential advantages of the nanoparticle delivery system in CRISPR genome editing. We will also propose potential strategies of CRISPR-based technology for therapeutic and industrial applications. Our review will differ in focus from previous reviews and advance the literature on the subject by (a) focusing on the challenges of the CRISPR/Cas9 delivery system; (b) focusing on the application of nanoparticle-based delivery of CRISPR components (Cas9 and sgRNA), such as lipids and polymeric vectors; (c) discussing the potential nanoparticle-based delivery approaches for CRISPR/Cas9 application. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.