CRISPR-Controlled DNA Hydrogels for Low-Trigger Programmability
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Solution Overview
Problem
Current DNA-responsive hydrogels require high concentrations of DNA triggers for actuation and involve extensive redesign for new trigger sequences, limiting their programmability.
Innovation Solution
Utilize CRISPR system components, specifically guide RNAs and CRISPR proteins like Cas9, Cas12a, to control the properties of hydrogels by cleaving nucleic acid molecules within the hydrogel structure, enabling responsive changes in properties such as release of molecules, nanoparticles, and live cells, and modulation of electrical and permeability properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If toehold strand-displacement or hairpin formation mechanisms are used in DNA-responsive hydrogels, then the hydrogels can be actuated by DNA triggers, but high concentrations of DNA triggers are required and extensive redesign is needed for new trigger sequences
Solution Approach 1:
The patent introduces CRISPR-Cas system as an intermediary between DNA triggers and hydrogel actuation. The guide RNA serves as a mediator that recognizes specific DNA sequences and recruits Cas proteins to cleave crosslinking DNA strands, enabling the hydrogel to respond to diverse DNA triggers without redesigning the hydrogel structure itself. This intermediary system decouples the trigger recognition function from the hydrogel matrix.
Solution Approach 2:
The patent creates a universal CRISPR-based platform where a single hydrogel formulation can respond to multiple different DNA trigger sequences by simply changing the guide RNA sequence. The Cas proteins and hydrogel matrix serve multiple functions: structural integrity, trigger recognition (via guide RNA), and actuation. This universal system eliminates the need for extensive redesign when adapting to new trigger sequences.
2Reliability
If high concentrations of DNA triggers are used for actuation, then the hydrogel can be activated, but the sensitivity and applicability of the system is limited
Solution Approach 1:
The patent replaces the mechanical toehold strand-displacement mechanism with the enzymatic CRISPR-Cas cleavage system. The Cas proteins act as molecular scissors that can cleave DNA crosslinking strands with high specificity and sensitivity, even at low trigger concentrations. This enzymatic mechanism substitutes the less sensitive mechanical displacement process, enabling reliable actuation at lower DNA trigger concentrations.
3Adaptability or versatility
If extensive hydrogel redesign is performed to adapt to new trigger sequences, then the hydrogel can respond to different triggers, but the time and resources required increase significantly
Solution Approach 1:
The patent introduces dynamic programmability through guide RNA sequences that can be easily modified to recognize different DNA triggers. Instead of statically designing different hydrogels for different triggers, the system dynamically adapts by changing the guide RNA sequence. This dynamic approach allows rapid reconfiguration of hydrogel specificity without time-consuming redesign of the hydrogel matrix itself.
Solution Approach 2:
The patent changes the key parameter for adaptability from hydrogel composition to guide RNA sequence. By modifying only the guide RNA sequence parameter while keeping the hydrogel matrix and Cas proteins constant, the system can rapidly adapt to new trigger sequences. This parameter change approach significantly reduces the time and resources required compared to comprehensive hydrogel redesign.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Achieves programmable and sensitive responses to user-defined nucleic acid inputs, enhancing the applicability of hydrogels in therapeutic, diagnostic, and sensing applications.
Implementation Method 1
the CRISPR component comprises at least one guide RNA; and the polynucleotide sequence of at least one nucleic acid molecule component in (i) is cleaved when contacted with the CRISPR component of (ii)
Data Source
AI summary
Disclosed herein are hydrogels comprising a polynucleotide-based structural component. Methods of altering a property of a hydrogel based on user-defined nucleic acid input sequences are also disclosed. In addition, various applications are described that utilize these hydrogels and methods.