Engineered materials for in vivo delivery of genome-editing machinery

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Abstract

Genome-editing technologies, such as CRISPR–Cas9, are promising for treating otherwise incurable genetic diseases. Great progress has been made for ex vivo genome editing; however, major bottlenecks exist in the development of efficient, safe and targetable in vivo delivery systems, which are needed for the treatment of many diseases. To achieve high efficacy and safety in therapeutic, in vivo genome editing, editing activities must be controlled spatially and temporally in the body, which requires novel materials, delivery strategies and control mechanisms. Thus, there is currently a tremendous opportunity for the biomaterials research community to develop in vivo delivery systems that overcome the problems of low editing efficiency, off-targeting effect, safety, and cell and tissue specificity. In this Review, we summarize delivery approaches and provide perspectives on the challenges and possible solutions, aiming to stimulate further development of engineered materials for in vivo delivery of genome-editing machinery.

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Fig. 1: Biological barriers to in vivo delivery from systemic circulation to cell nucleus.
Fig. 2: Viral base in vivo delivery of genome-editing machinery.
Fig. 3: Examples of material systems for in vivo delivery of genome-editing machinery.
Fig. 4: Delivery strategies to overcome challenges in the efficiency, specificity and safety of in vivo delivery of genome-editing machinery.

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Acknowledgements

This work was supported by the Cancer Prevention and Research Institute of Texas (RR140081 to G.B.), the National Institutes of Health (R01EB026893 to S.T., UG3TR002863 to K.L. and UG3HL151545 to G.B.) and Defense Advanced Research Projects Agency (HR0011-19-2-0009 to K.L.).

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All authors contributed to the discussion and writing of this manuscript.

Correspondence to Gang Bao.

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