(Press-News.org) DURHAM, N.C. – CRISPR gene editing is a breakthrough that has been used to treat diseases such as sickle cell anemia, leukemia and genetic disorders, but it has challenges that limit its broad utility.
Identifying the root of those issues led a research team at Duke Health to find an improved approach to gene editing that expands its functionality.
In work appearing online June 29 in the journal Cell Chemical Biology, the researchers lay out a new way to identify diverse CRISPR RNA variants that can specifically home in on challenging areas of DNA to target for editing. The new approach opens up more of the genome for editing, enabling the repair of mutations associated with more diseases.
“CRISPR is great, but there are a lot of places within the human genome that can’t be edited well,” said senior author Bruce Sullenger, Ph.D., the Joseph W. and Dorothy W. Beard Distinguished Professor of Experimental Surgery at Duke University School of Medicine. Sullenger is also a professor in the departments of Pharmacology and Cancer Biology, Neurosurgery, Cell Biology and Biomedical Engineering.
“This work started from ground zero to understand and address that issue using large libraries of different CRISPR RNAs as well as informatics to see if we could get these editing tools to more places in the genome so that they can be edited and repaired as needed,” Sullenger said.
Sullenger and colleagues -- notably first author Korie Bush, Ph.D., who launched the study as a graduate student in Sullenger’s lab -- sought to improve the process CRISPR relies on to guide RNA to the right location on DNA and facilitate the deletion or repair in that region.
More often than not, the guide, which is an RNA molecule, presents a problem -- it may not fold exactly right or it’s otherwise corrupted, so the editing or deletion process cannot occur. Typically when that happens, the guide RNA must be swapped out for a new one and the genome cannot be targeted in the right spot.
The Duke team instead found a way to salvage a dysfunctional guide RNA, which actually has two components that have to work well together: an RNA sequence that recognizes the DNA target site and a scaffolding sequence that holds the enzyme in place to cleave the DNA at the right juncture.
They found multiple RNA sequences that revived the integrity of the scaffolding, demonstrating that CRISPR gene editing technology is much more adaptable than previously believed.
“We found lots of ways to change the system that yield combinations with enhanced editing efficiencies at various target sites,” Bush said. “The process is more malleable than we thought – we made hundreds of thousands of guide RNAs. If you need two pieces for the process to work well and you have so many more options to choose from, you can find a combination that works best.”
Sullenger said the finding should lead to safer and more effective ways of applying CRISPR technology as a therapy.
“This is like an improvement in word processing that enables you to easily find and edit any error in the text, rather than only being able to edit certain portions of a text effectively,” Sullenger said. “Especially when coupled with informatics, it should lead to an acceleration of breakthroughs for treating diseases.”
In addition to Sullenger and Bush, study authors include Giulia Corsi, Amy C. Yan, Keith Haynes, Juliana M. Layzer, Jonathan H. Zhou, Telmo Llanga, and Jan Gorodkin.
The research received support from the National Institutes of Health (UG3 TR002852), the
Independent Research Foundation Denmark (9041-00317B) and the Novo Nordisk
Foundation (NNF21OC0068988).
###
END
Water fasts — where people consume nothing but water for several days — might help you lose weight, but it’s unclear how long you’ll keep it off, according to research from the University of Illinois Chicago. And the other metabolic benefits of water fasts, such as lower blood pressure and improved cholesterol, seem to disappear soon after the fast ends, the researchers found.
However, there do not appear to be any serious adverse effects for those who do a water fast or a similar kind of fast where people consume a very small number of calories a day, said Krista Varady, professor of kinesiology and nutrition, who led the research, ...
In light of climate change and the impending transition to clean energy, many long-standing programs to address energy insecurity need to be refreshed. A new paper published online in the journal Health Affairs provides growing documentation of the connections between energy insecurity and poor health. The paper, by Diana Hernandez, PhD, associate professor of sociomedical sciences at Columbia University Mailman School of Public Health, also offers an overview of current policy initiatives and discusses ways that current policies can be improved upon.
The average U.S. household allocates 3.1 percent of its income to energy expenses but for low-income households, ...
Rockville, MD – The latest journal impact factors and rankings reflect the high-quality research that is published each year by the American Society for Nutrition (ASN).
Scopus recently ranked Advances in Nutrition the number one journal in the Nutrition and Dietetics field. The Society’s newest journal, Current Developments in Nutrition, surpassed expectations with an excellent inaugural impact factor of 4.8 confirming its promising future.
“I am delighted to receive such a superb first impact factor,” stated Jack Odle, PhD, William Neal Reynolds Distinguished Professor at North Carolina State University and Editor-in-Chief of Current ...
Glenview, Illinois – The American College of Chest Physicians® (CHEST) recently released a new clinical guideline on antithrombotic therapy in arterial thrombosis andthromboembolism in COVID-19. Published in the journal CHEST®, the guideline contains 11 evidence-based recommendations to improve risk-evaluation and to assist in determining the course of treatment.
While there are guidelines for the management of COVID-19-related coagulopathy for venous thromboembolism (VTE), a recent large cohort study showed ...
The College of Pharmacy at the University of Tennessee Health Science Center is now ranked No. 6 in annual research funding from the National Institutes of Health, according to a new listing published by the American Association of Colleges of Pharmacy of its approximately 140 member institutions.
“The ranking of No. 6 in NIH funding for federal fiscal year 2022 is external validation for the UTHSC College of Pharmacy’s standing as one of the leading institutions in research among the 142 U.S. pharmacy schools,” said Bernd Meibohm, ...
WASHINGTON — Researchers report a new single-photon Raman lidar system that operates underwater and can remotely distinguish various substances. They also show that the new system can detect the thickness of the oil underwater up to 12 m away, which could be useful for detecting oil spills.
“Differentiating substances in water and detecting their distribution characteristics in the ocean are of great significance for marine monitoring and scientific research,” said research team leader Mingjia Shangguan from Xiamen University in China. “For instance, the remote sensing of underwater oil that we ...
Oak Ridge National Laboratory researchers have developed a method to simplify one step of radioisotope production — and it’s faster and safer.
ORNL produces several radionuclides from irradiated radium-226 targets, including actinium-227 and thorium-228, both used in cancer treatments. Continuously improving isotopes for human health is one of the lab’s missions.
Currently, it takes workers two weeks to prepare radium-226 targets for irradiation in the High Flux Isotope Reactor. The targets are exposed to radiation throughout the process, which involves pressing radium carbonate aluminum composite into 10 pellets — one each day — and sealing ...
About The Study: This systematic review and meta-analysis including 41 studies and 7,800 participants found that psychosocial interventions were associated with decreased health care use in most health services and increased use of outpatient care. The greatest health care decrease was among caregivers and individuals with mental illnesses and in interventions delivered 1-on-1 by health professionals.
Authors: Neta HaGani, M.S.W., of the University of Sydney in Sydney, Australia, is the corresponding author.
To ...
New York, NY—June 29, 2023—The data centers and high-performance computers that run artificial intelligence programs, such as large language models, aren’t limited by the sheer computational power of their individual nodes. It’s another problem — the amount of data they can transfer among the nodes — that underlies the “bandwidth bottleneck” that currently limits the performance and scaling of these systems.
The nodes in these systems can be separated by more than one kilometer. Since metal wires dissipate electrical signals as heat when transferring data at high speeds, these systems transfer data via fiber-optic ...
Have you ever felt the strong sensation that someone is behind you, so intense that you turn around, only to see that no-one is there? This is a 'presence hallucination’. Presence hallucinations are particularly frequent but underreported in patients with Parkinson’s disease and may appear early on in the course of the disease. They are sometimes ignored by the patient, by clinicians, or brushed off as a simple side-effect of medication.
Now, EPFL scientists have found that patients recently diagnosed with Parkinson’s disease and who have early hallucinations are ...
