Smart materials change properties in response to specific DNA sequences; could be used in a variety of devices.
The CRISPR genome-editing system is best-known for its potential to correct disease-causing mutations and add new genes into living cells. Now, a team from MIT and Harvard University has deployed CRISPR for a completely different purpose: creating novel materials, such as gels, that can change their properties when they encounter specific DNA sequences.
The researchers showed they could use CRISPR to control electronic circuits and microfluidic devices, and to release drugs, proteins, or living cells from gels. Such materials could be used to create diagnostic devices for diseases such as Ebola, or to deliver treatments for diseases such as irritable bowel disease.
“This study serves as a nice starting point for showing how CRISPR can be utilized in materials science for a really wide range of applications,” says James Collins, the Termeer Professor of Medical Engineering and Science in MIT’s Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering, and the senior author of the study.
The lead authors of the study, which appears in the Aug. 22 online edition of Science, are MIT graduate students Max Atti English, Luis Soenksen, and Raphael Gayet, and postdoc Helena de Puig.
CRISPR is based on DNA-cutting proteins called Cas enzymes, which bind to short RNA guides that direct them to specific areas of the genome. Cas cuts DNA in those locations, deleting a gene or allowing new genetic sequences to be introduced.
Over the past several years, much research has been devoted to developing CRISPR as a gene-editing tool for treating disease by cutting out or repairing faulty genes. The MIT and Harvard team set out to adapt it for creating materials that could respond to external cues such as the presence of a certain sequence of DNA.
For this work, they used an enzyme known as Cas12a, which can be programmed to bind to specific sequences of double-stranded DNA by simply changing the guide RNA sequence that is given along with the enzyme. Once Cas12a encounters a target DNA sequence, also called a trigger, it cleaves the double-stranded DNA and transforms into an enzyme that can slice any single-stranded DNA it encounters.
“By incorporating DNA into materials, you can use this enzyme to control the properties of the materials in response to a specific biological cue in the environment,” English says.
The researchers took advantage of this to design gels that incorporate single-stranded DNA in key functional or structural roles. In one example, they created a gel made of polyethylene glycol (PEG) and used DNA to anchor enzymes or other large biomolecules to the gel. When activated by a trigger sequence, Cas12a cuts the DNA anchors, releasing the payload.
That type of gel could be useful for releasing therapeutic compounds such as drugs or growth factors, the researchers say. In another example, they created an acrylamide gel in which single-stranded DNA forms an integral part of the gel structure. In that case, when Cas12a is activated by the trigger, the entire gel breaks down, enabling the release of larger cargoes such as cells or nanoparticles.
“In that context, we consider the single-stranded DNA as a structural scaffold,” Gayet says. “The enzyme is able to catalyze the cleavage of the single-stranded DNA, which acts as a structural linker, and release all of those molecules.”
The researchers are now exploring the possibility of using this approach to deliver engineered bacterial cells to help treat gastrointestinal diseases.
The researchers also created two CRISPR-controlled diagnostic devices, one based on an electronic circuit and the other on a microfluidic chip.
To create the electronic circuit, the researchers designed a gel that includes single-stranded DNA and a material called carbon black, which conducts electricity. When attached to the surface of an electrode, this conductive gel allows electrical current to flow. However, if Cas12a is activated by a trigger sequence, such as a strand of viral DNA from a blood sample, the gel becomes detached from the electrode and current stops flowing.
For their microfluidic sensor, the researchers created a DNA-containing gel that acts as a valve that controls the flow of a solution through the microfluidic channel. If the solution contains a blood sample with a target DNA sequence, the gel breaks down, turning off the valve, and the solution stops flowing. This microfluidic sensor can be connected to an RFID chip, allowing it to wirelessly transmit the results of the test.
“A health care worker can be monitoring dozens of patients, and the presence or absence of the Ebola trigger will automatically relay a binary signal,” Soenksen says.
While the researchers used fluid samples containing Ebola virus RNA to test this approach, it could also be adapted to detect other infectious diseases, as well as cancer cells circulating in a patient’s bloodstream.
Philip LeDuc, a professor of mechanical engineering at Carnegie Mellon University, describes the work as “tremendously creative.”
“This is a very non-obvious intersection of two different fields, and the influence of this work will be far-reaching,” says LeDuc, who was not involved in the study. “This transdisciplinary work may enable an entire new generation of approaches for applications from building artificial organs to improving the environment.”
Learn more: Using CRISPR to program gels with new functions
The Latest on: CRISPR
via Google News
The Latest on: CRISPR
- Cathie Wood Sheds $5M In CRISPR Therapeutics, Scoops Up These Biotech Stocks Insteadon August 4, 2022 at 10:09 pm
Cathie Wood-led Ark Investment Management on Thursday sold 70,723 shares of gene editing company CRISPR Therapeutics AG (NASDAQ: CRSP), valued at over $5.58 million, via its flagship fund.
- Citigroup Increases CRISPR Therapeutics (NASDAQ:CRSP) Price Target to $83.00on August 3, 2022 at 2:24 am
CRISPR Therapeutics (NASDAQ:CRSP – Get Rating) had its target price lifted by Citigroup from $53.00 to $83.00 in a report issued on Tuesday morning, The Fly reports. The firm currently has a neutral ...
- Steward Partners Investment Advisory LLC Raises Holdings in CRISPR Therapeutics AG (NASDAQ:CRSP)on August 3, 2022 at 1:22 am
Steward Partners Investment Advisory LLC raised its stake in shares of CRISPR Therapeutics AG (NASDAQ:CRSP – Get Rating) by 155.5% during the first quarter, Holdings Channel.com reports. The ...
- First CRISPR cure for high cholesterol enters human trial phaseon August 2, 2022 at 3:13 pm
Researchers have managed to create a cure for high cholesterol. After seeing success in animals, the cure has moved to its first human trials.
- Where CRISPR Therapeutics Stands With Analystson August 2, 2022 at 10:29 am
In the last 3 months, 19 analysts have offered 12-month price targets for CRISPR Therapeutics. The company has an average price target of $98.0 with a high of $168.00 and a low of $46.00. Below is a ...
- CRISPR Gene Editing Market Size is projected to reach USD 14.80 Billion by 2030, growing at a CAGR of 29.80%: Straits Researchon August 1, 2022 at 9:40 am
The global CRISPR Gene Editing Market was valued USD 1.09 billion in 2021 and is predicted to reach USD 14.80 billion by 2030, increasing at a CAGR of 29.80% from 2022 to 2030. North America dominated ...
- Where Will CRISPR Therapeutics Be in 1 Year?on July 31, 2022 at 8:00 am
CRISPR Therapeutics looks increasingly likely to launch an important product on the market within the next year. The company will also announce data from some of its ongoing clinical trials. If ...
- Intellia Therapeutics Is Pushing CRISPR-Based Therapy Forward, Slowly But Surelyon July 29, 2022 at 10:31 pm
Intellia’s recent data from its Regeneron collaboration for CRISPR-based NTLA-2001 shows a durable response to the lead in vivo genome editing candidate.
- Using CRISPR to Lift the Lid on Probioticson July 26, 2022 at 5:49 am
In this interview, we speak to Echo Pan, a Ph.D. student from North Carolina State University about her latest research that used CRISPR to uncover more on probiotics.
- Crispr Therapeutics' Continued Progress Warrants A Buyon July 25, 2022 at 1:23 pm
Crispr Therapeutics continues to make progress toward submitting a global regulatory filing for CTX001. Click here to read why shares are a buy.
via Bing News