Non-viral delivery of CRISPR/Cas9 complex using CRISPR-GPS nanocomplexes

Piyush K Jain; Justin H Lo; Santosh Rananaware; Marco Downing; Apekshya Panda; Michelle Tai; Srivatsan Raghavan; Heather E Fleming; Sangeeta N Bhatia

doi:10.1039/c9nr01786k

Non-viral delivery of CRISPR/Cas9 complex using CRISPR-GPS nanocomplexes

Nanoscale. 2019 Nov 28;11(44):21317-21323. doi: 10.1039/c9nr01786k. Epub 2019 Oct 31.

Authors

Piyush K Jain¹, Justin H Lo², Santosh Rananaware³, Marco Downing³, Apekshya Panda⁴, Michelle Tai⁵, Srivatsan Raghavan⁶, Heather E Fleming⁷, Sangeeta N Bhatia⁸

Affiliations

¹ Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, USA and Marble Center for Cancer Nanomedicine, Institute for Medical Engineering & Science, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and UF Health Cancer Center, University of Florida, Gainesville, FL 32608. jainp@ufl.edu.
² Marble Center for Cancer Nanomedicine, Institute for Medical Engineering & Science, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
³ Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, USA.
⁴ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02139, USA.
⁵ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁶ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA and Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02139, USA.
⁷ Marble Center for Cancer Nanomedicine, Institute for Medical Engineering & Science, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁸ Marble Center for Cancer Nanomedicine, Institute for Medical Engineering & Science, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02139, USA and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA and Howard Hughes Medical Institute, Cambridge, MA 02139, USA. sbhatia@mit.edu.

Abstract

There is a critical need for the development of safe and efficient delivery technologies for CRISPR/Cas9 to advance translation of genome editing to the clinic. Non-viral methods that are simple, efficient, and completely based on biologically-derived materials could offer such potential. Here we report a simple and modular tandem peptide-based nanocomplex system with cell-targeting capacity that efficiently combines guide RNA (sgRNA) with Cas9 protein, and facilitates internalization of sgRNA/Cas9 ribonucleoprotein complexes to yield robust genome editing across multiple cell lines.

MeSH terms

CRISPR-Cas Systems*
Gene Editing*
Gene Transfer Techniques*
HeLa Cells
Humans

Abstract

MeSH terms

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