Wei Tuo, Cheng Qiang, Farbiak Lukas, Anderson Daniel G, Langer Robert, Siegwart Daniel J
Department of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
ACS Nano. 2020 Aug 25;14(8):9243-9262. doi: 10.1021/acsnano.0c04707. Epub 2020 Jul 22.
CRISPR/Cas9-based genome editing has quickly emerged as a powerful breakthrough technology for use in diverse settings across biomedical research and therapeutic development. Recent efforts toward understanding gene modification methods have led to substantial improvements in genome editing efficiency. Because disease targets for genomic correction are often localized in specific organs, realization of the full potential of genomic medicines will require delivery of CRISPR/Cas9 systems targeting specific tissues and cells directly . In this Perspective, we focus on progress toward delivery of CRISPR/Cas components. Viral and nonviral delivery systems are both promising for gene editing in diverse tissues local injection and systemic injection. We describe the various viral vectors and synthetic nonviral materials used for gene editing and applications to research and therapeutic models, and summarize opportunities and progress to date for both methods. We also discuss challenges for viral delivery, including overcoming limited packaging capacity, immunogenicity associated with multiple dosing, and the potential for off-target effects, and nonviral delivery, including efforts to increase efficacy and to expand utility of nonviral carriers for use in extrahepatic tissues and cancer. Looking ahead, additional advances in the safety and efficiency of viral and nonviral delivery systems for tissue- and cell-type-specific gene editing will be required to enable broad clinical translation. We provide a summary of current delivery systems used for genome editing, organized with respect to route of administration, and highlight immediate opportunities for biomedical research and applications. Furthermore, we discuss current challenges for delivery of CRISPR/Cas9 systems to guide the development of future therapies.
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