Programmable CRISPR-responsive smart materials

Max A English; Luis R Soenksen; Raphael V Gayet; Helena de Puig; Nicolaas M Angenent-Mari; Angelo S Mao; Peter Q Nguyen; James J Collins

doi:10.1126/science.aaw5122

Programmable CRISPR-responsive smart materials

Science. 2019 Aug 23;365(6455):780-785. doi: 10.1126/science.aaw5122.

Authors

Max A English^#^{1

2}, Luis R Soenksen^#^{2

3

4}, Raphael V Gayet^#^{1

2

5}, Helena de Puig^#^{2

4}, Nicolaas M Angenent-Mari^#^{1

2

4}, Angelo S Mao^#^{2

4

6}, Peter Q Nguyen^{4

6}, James J Collins^{7

2

4

8

9

10}

Affiliations

¹ Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
² Institute for Medical Engineering and Science, MIT, Cambridge, MA 02139, USA.
³ Department of Mechanical Engineering, MIT, Cambridge, Cambridge, MA 02139, USA.
⁴ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
⁵ Microbiology Graduate Program, MIT, Cambridge, MA 02139, USA.
⁶ School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
⁷ Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. jimjc@mit.edu.
⁸ Synthetic Biology Center, MIT, Cambridge, MA 02139, USA.
⁹ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
¹⁰ Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA 02139, USA.

^# Contributed equally.

PMID: 31439791
DOI: 10.1126/science.aaw5122

Abstract

Stimuli-responsive materials activated by biological signals play an increasingly important role in biotechnology applications. We exploit the programmability of CRISPR-associated nucleases to actuate hydrogels containing DNA as a structural element or as an anchor for pendant groups. After activation by guide RNA-defined inputs, Cas12a cleaves DNA in the gels, thereby converting biological information into changes in material properties. We report four applications: (i) branched poly(ethylene glycol) hydrogels releasing DNA-anchored compounds, (ii) degradable polyacrylamide-DNA hydrogels encapsulating nanoparticles and live cells, (iii) conductive carbon-black-DNA hydrogels acting as degradable electrical fuses, and (iv) a polyacrylamide-DNA hydrogel operating as a fluidic valve with an electrical readout for remote signaling. These materials allow for a range of in vitro applications in tissue engineering, bioelectronics, and diagnostics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acrylic Resins / chemistry
Bacterial Proteins / chemistry*
Biocompatible Materials / chemistry*
Biosensing Techniques*
CRISPR-Associated Proteins / chemistry*
Cells / chemistry
Cross-Linking Reagents / chemistry
DNA / chemistry*
DNA Cleavage
DNA, Single-Stranded / chemistry
Endodeoxyribonucleases / chemistry*
Hydrogels / chemistry*
Lab-On-A-Chip Devices
Nanoparticles / chemistry
Pathology, Molecular*
Permeability
Polyethylene Glycols / chemistry
Tissue Engineering*

Substances

Acrylic Resins
Bacterial Proteins
Biocompatible Materials
CRISPR-Associated Proteins
Cross-Linking Reagents
DNA, Single-Stranded
Hydrogels
Polyethylene Glycols
polyacrylamide
DNA
Cas12a protein
Endodeoxyribonucleases