Corporate Banner
Satellite Banner
RNAi
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

An Easier Way to Control Genes

Published: Tuesday, September 03, 2013
Last Updated: Tuesday, September 03, 2013
Bookmark and Share
New method for turning genes on and off could enable more complex synthetic biology circuits.

MIT researchers have shown that they can turn genes on or off inside yeast and human cells by controlling when DNA is copied into messenger RNA — an advance that could allow scientists to better understand the function of those genes.

The technique could also make it easier to engineer cells that can monitor their environment, produce a drug or detect disease, says Timothy Lu, an assistant professor of electrical engineering and computer science and biological engineering and the senior author of a paper describing the new approach in the journal ACS Synthetic Biology.

“I think it’s going to make it a lot easier to build synthetic circuits,” says Lu, a member of MIT’s Synthetic Biology Center. “It should increase the scale and the speed at which we can build a variety of synthetic circuits in yeast cells and mammalian cells.”

The new method is based on a system of viral proteins that have been exploited recently to edit the genomes of bacterial and human cells. The original system, called CRISPR, consists of two components: a protein that binds to and slices DNA, and a short strand of RNA that guides the protein to the right location on the genome.

“The CRISPR system is quite powerful in that it can be targeted to different DNA binding regions based on simple recoding of these guide RNAs,” Lu says. “By simply reprogramming the RNA sequence you can direct this protein to any location you want on the genome or on a synthetic circuit.”

Lead author of the paper is Fahim Farzadfard, an MIT graduate student in biology. Samuel Perli, a graduate student in electrical engineering and computer science, is also an author.

Targeting transcription

In previous studies, CRISPR has been used to snip out pieces of a gene to disable it or replace it with a new gene. Lu and his colleagues decided to use the CRISPR system for a different purpose: controlling gene transcription, the process by which a sequence of DNA is copied into messenger RNA (mRNA), which carries out the gene’s instructions.

Transcription is tightly regulated by proteins called transcription factors. These proteins bind to specific DNA sequences in the gene’s promoter region and either recruit or block the enzymes needed to copy that gene into mRNA.

For this study, the researchers adapted the CRISPR system to act as a transcription factor. First, they modified the usual CRISPR protein, known as Cas9, so that it could no longer snip DNA after binding to it. They also added to the protein a segment that activates or represses gene expression by modulating the cell’s transcriptional machinery.

To get Cas9 to the right place, the researchers also delivered to the target cells a gene for an RNA guide that corresponds to a DNA sequence on the promoter of the gene they want to activate.

The researchers showed that once the RNA guide and the Cas9 protein join together inside the target cell, they accurately target the correct gene and turn on transcription. To their surprise, they found that the same Cas9 complex could also be used to block gene transcription if targeted to a different part of the gene.

“This is nice in that it allows you do to positive and negative regulation with the same protein, but with different guide RNAs targeted to different positions in the promoter,” Lu says.

‘A lot of flexibility’

The new system should be much easier to use than two other recently developed transcription-control systems based on DNA-binding proteins known as zinc fingers and transcription activator-like effector nucleases (TALENs), Lu says. Although they are effective, designing and assembling the proteins is time-consuming and expensive.

“There’s a lot of flexibility with CRISPR, and it really comes from the fact that you don’t have to spend any more time doing protein engineering. You can just change the nucleic acid sequence of the RNAs,” Lu says.

The researchers also designed the transcription-control system so that it can be induced by certain small molecules that can be added to the cell, such as sugars. To do this, they engineered the genes for the guide RNAs so that they are only produced when the small molecule is present. Without the small molecule, there is no guide RNA and the targeted gene is undisturbed.

This type of control could be useful for studying the role of naturally occurring genes by turning them on and off at specific points during development or disease progression, Lu says.

Lu is now working on building more advanced synthetic circuits to perform applications such as making decisions based on several inputs from a cell’s environment. “We’d like to be able to scale this up and demonstrate the most complex circuits that anyone’s ever built in yeast and mammalian cells,” he says.

The research was funded by the Defense Advanced Research Projects Agency, the National Institutes of Health New Innovator Award and the National Science Foundation.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Curing Disease by Repairing Faulty Genes
New delivery method boosts efficiency of CRISPR genome-editing system.
Wednesday, February 03, 2016
No More Insulin Injections?
Encapsulated pancreatic cells offer possible new diabetes treatment.
Tuesday, January 26, 2016
Engineering Foe into Friend
Bose Grant awardee Jacquin Niles aims to repurpose the malaria parasite for drug delivery.
Monday, January 25, 2016
Supply Chain
Chemists discover how a single enzyme maintains a cell’s pool of DNA building blocks.
Wednesday, January 13, 2016
How Cancer Cells Spread
Study offers new targets for drugs that may prevent cancer from spreading.
Thursday, December 17, 2015
Delivering microRNAs for Cancer Treatment
Scientists exploit gene therapy to shrink tumors in mice with an aggressive form of breast cancer.
Wednesday, December 09, 2015
Using Ultrasound to Improve Drug Delivery
New approach could aid in treatment of inflammatory bowel disease.
Friday, October 23, 2015
Drug-Resistance Mechanism in Tumor Cells Unravelled
Targeting the RNA-binding protein that promotes resistance could lead to better cancer therapies.
Friday, October 23, 2015
Biologists Find Unexpected Role for Amyloid-Forming Protein
Yeast protein could offer clues to how Alzheimer’s plaques form in the brain.
Monday, September 28, 2015
Viruses Join Fight Against Harmful Bacteria
Engineered viruses could combat human disease and improve food safety.
Friday, September 25, 2015
Targeting DNA
Protein-based sensor could detect viral infection or kill cancer cells.
Tuesday, September 22, 2015
A Metabolic Master Switch Underlying Human Obesity
Researchers find pathway that controls metabolism by prompting fat cells to store or burn fat.
Friday, August 21, 2015
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Friday, July 31, 2015
Firms “Under-invest” in Long-Term Cancer Research
Tweaks to the R&D pipeline could create new drugs and greater social benefit.
Thursday, July 30, 2015
Nanoparticles Can Clean Up Environmental Pollutants
Researchers have found that nanomaterials and UV light can “trap” chemicals for easy removal from soil and water.
Thursday, July 23, 2015
Scientific News
Cancer Cells Kill Off Healthy Neighbours
Cancer cells create space to grow by killing off surrounding healthy cells, according to UK researchers working with fruit flies.
Cancer Drug Target Visualized at Atomic Resolution
New study using cryo-electron microscopy shows how potential drugs could inhibit cancer.
Genetic Mechanism Behind Cancer-Causing Mutations
Researchers at Indiana University has identified a genetic mechanism that is likely to drive mutations that can lead to cancer.
Future of Medicine Could be Found in a Tiny Crystal Ball
A Drexel University materials scientist has discovered a way to grow a crystal ball in a lab. Not the kind that soothsayers use to predict the future, but a microscopic version that could be used to encapsulate medication in a way that would allow it to deliver its curative payload more effectively inside the body.
"Gene Fusion" Drives Childhood Brain Cancers
Study co-led by Penn scientists highlights potential targets for future cancer therapies.
Enzyme Links Age-Related Inflammation, Cancer
Researchers have shown that an enzyme key to regulating gene expression -- and also an oncogene when mutated -- is critical for the expression of numerous inflammatory compounds that have been implicated in age-related increases in cancer and tissue degeneration.
Viral Gene Editing System Corrects Genetic Liver Disease
Penn study has implications for developing safe therapies for an array of rare diseases via new gene cut-and-paste methods.
Improving Delivery of Poorly Soluble Drugs Using Nanoparticles
A technology that could forever change the delivery of drugs is undergoing evaluation by the Technology Evaluation Consortium™ (TEC). Developed by researchers at Northeastern University, the technology is capable of creating nanoparticle structures that could deliver drugs into the bloodstream orally – despite the fact that they are normally poorly soluble.
Curing Disease by Repairing Faulty Genes
New delivery method boosts efficiency of CRISPR genome-editing system.
'Junk' DNA Plays Role in Preventing Breast Cancer
Supposed "junk" DNA, found in between genes, plays a role in suppressing cancer, according to new research by Universities of Bath and Cambridge.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!