PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Library that can determine resistance

Genetic screening identifies genes driving resistance with a guide RNA library

2013-12-27
(Press-News.org) Contact information: Aileen Sheehy
press.office@sanger.ac.uk
44-012-234-92384
Wellcome Trust Sanger Institute
Library that can determine resistance Genetic screening identifies genes driving resistance with a guide RNA library Researchers have developed a method to create a comprehensive library of mutations across all genes in the mouse genome. This library can be used to examine the role of every gene in different cell types.

CRISPR technology uses the DNA-cutting enzyme Cas9, with the help of a guide RNA sequence, to find and modify genetic targets. Scientists can easily engineer multiple new guide RNAs using standard molecular biology techniques. This makes for a much faster and efficient method to modify the genome of any cell type in any species.

The team found that a remarkable 50 of 52 guide RNAs tested successfully cut both copies of the genes. The extremely high success rate for these engineered guide RNAs seems to be consistent across many cell types, which led them to create a library of guide RNAs targeting every gene in the mouse genome.

"CRISPR technology is revolutionising how we study the behaviour of cells," says Dr Kosuke Yusa, lead author from the Wellcome Trust Sanger Institute. "We've developed a thorough library that can be used by other researchers to study the role of any gene. We can create a library of this type for any cell or any species."

The team has engineered a library of nearly 90,000 of these guide RNAs that can be used to target and modify every gene in the mouse genome, and created mutant stem cell libraries. They subjected the mutant libraries to a genetic screen against a bacterial toxin, Clostridium septicum alpha-toxin, to better understand how resistance can occur: This agent has toxic effects on every cell type.

The team targeted 26 genes that are known to be associated with the synthesis of the receptors of this bacterial toxin. They revealed that 17 of these genes were responsible for resistance. Importantly, they also identified previously unknown genes whose mutations confer with resistance to this toxic agent.

The team will now use this library to create mutations in cancer cell lines. A major problem with cancer drugs is that often cells can quickly acquire resistance and reject the treatment. By screening for genes that have lost all function through mutation, the team can determine what genes are involved in acquiring resistance to cancer treatments and thus find a clinical target.

### Notes to Editors Publication Details Hiroko Koike-Yusa, Yilong Li, E-Pien Tan, Martin Del Castillo Velasco-Herrera and Kosuke Yusa (2013). 'Recessive genetic screening with a genome-wide lentiviral CRISPR-guide RNA library'

Advanced online publication in Nature Biotechnology 17 Jan. doi:10.1038/nbt.2800

Funding This work was supported by Wellcome Trust

Participating Centres Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK

Selected Websites

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. http://www.sanger.ac.uk

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests. http://www.wellcome.ac.uk

Contact details Don Powell Media Manager
Wellcome Trust Sanger Institute
Hinxton, Cambridge, CB10 1SA, UK
Tel +44 (0)1223 496 928
Mobile +44 (0)7753 7753 97
Email press.office@sanger.ac.uk

End of Notes to Editors END


ELSE PRESS RELEASES FROM THIS DATE:

Hypoxic preconditioning stimulates angiogenesis in ischemic penumbra after ACI

2013-12-27
Hypoxic preconditioning stimulates angiogenesis in ischemic penumbra after ACI Hypoxic preconditioning has been shown to have protective effects against acute cerebral infarction. To investigate the protective mechanisms of hypoxic preconditioning in relation ...

Transient receptor potential channel A1 may contribute to hyperalgesia

2013-12-27
Transient receptor potential channel A1 may contribute to hyperalgesia Transient receptor potential channel A1 is one of the important transducers of noxious stimuli in the primary afferents, which may contribute to generation of neurogenic inflammation and hyperalgesia. ...

An expert consensus on acute thoracolumbar spine and spinal cord injury in China

2013-12-27
An expert consensus on acute thoracolumbar spine and spinal cord injury in China The early management of acute thoracolumbar spine and spinal cord injury is one of the most difficult tasks when treating trauma cases. To standardize the evaluation and treatment of ...

Motor excitability predicts working memory

2013-12-27
Motor excitability predicts working memory Humans with a high motor excitability have a better working memory than humans with a low excitability. This was shown in a study conducted by scientists from the Transfacultary Research Platform at the University of Basel. By measuring ...

Breast cancer patients experience fewer side effects from anticancer drug

2013-12-27
Breast cancer patients experience fewer side effects from anticancer drug A new analysis has found that both real and sham acupuncture treatments may help alleviate side effects of drugs commonly used to treat breast cancer. Published early online in CANCER, a peer-reviewed journal ...

Democracy pays

2013-12-27
Democracy pays Majority wants both punishment for tax evaders and things to go fine for themselves This news release is available in German. In relatively large communities, individuals do not always obey the rules and often exploit the willingness ...

Antibiotics before heart surgery protect against infection

2013-12-27
Antibiotics before heart surgery protect against infection Preoperative antibiotics administered within two hours of operation optimal for protection CHICAGO (December 23, 2013) – A new study found preoperative antibiotic therapy administered within ...

Infectious diarrhea germs stick to healthcare worker hands

2013-12-27
Infectious diarrhea germs stick to healthcare worker hands Study shows healthcare workers' hands contaminated with C. difficile after routine care CHICAGO (December 23, 2013) – A new study finds nearly one in four healthcare workers' hands were ...

Role of chronic medical conditions in readmissions

2013-12-27
Role of chronic medical conditions in readmissions Researchers cite identification and monitoring of known underlying chronic medical conditions as opportunities to reduce readmission rates and improve patient safety Researchers cite identification and ...

Resistance makes waves

2013-12-27
Resistance makes waves There is a growing understanding of the conditions required for superconductivity and how it can be achieved at realistic temperatures This news release is available in German. Even physics can give pointers for energy saving. ...

LAST 30 PRESS RELEASES:

Innovative oncolytic virus and immunotherapy combinations pave the way for advanced cancer treatment

New insights into energy metabolism and immune dynamics could transform head and neck cancer treatment

Pennington Biomedical’s Dr. Steven Heymsfield named LSU Boyd Professor – LSU’s highest faculty honor

Study prompts new theory of human-machine communication

New method calculates rate of gene expression to understand cell fate

Researchers quantify rate of essential evolutionary process in the ocean

Innovation Crossroads companies join forces, awarded U.S. Air Force contract

Using new blood biomarkers, USC researchers find Alzheimer’s disease trial eligibility differs among various populations

Pioneering advances in in vivo CAR T cell production

Natural medicines target tumor vascular microenvironment to inhibit cancer growth

Coral-inspired pill offers a new window into the hidden world of the gut

nTIDE September2025 Jobs Report: Employment for people with disabilities surpasses prior high

When getting a job makes you go hungry

Good vibrations could revolutionize assisted reproductive technology

More scrutiny of domestic fishing fleets at ports could help deter illegal fishing

Scientists transform plastic waste into efficient CO2 capture materials

Discovery of North America’s role in Asia’s monsoons offers new insights into climate change

MD Anderson and Phoenix SENOLYTIX announce strategic cross-licensing agreement to enhance inducible switch technologies for cell and gene therapies

Researchers discover massive geo-hydrogen source to the west of the Mussau Trench

Even untouched ecosystems are losing insects at alarming rates, new study finds

Adaptive visible-infrared camouflage with wide-range radiation control for extreme ambient temperatures

MD Anderson research highlights for September 5, 2025

Physicists create a new kind of time crystal that humans can actually see

Reminder: Final media invitation for EPSC-DPS2025 and details of media briefings on RAMSES and Juno missions

Understanding orderly and disorderly behavior in 2D nanomaterials could enable bespoke design, tailored by AI

JAMA Network launches JAMA+ Women's Health

Surface plasmon driven atomic migration mediated by molecular monolayer

ERC Starting Grant for five University of Groningen scientists

AI turns printer into a partner in tissue engineering

What climate change means for the Mediterranean Sea

[Press-News.org] Library that can determine resistance
Genetic screening identifies genes driving resistance with a guide RNA library