Breaking News
January 20, 2019 - Liver Transplant Survival May Improve With Race Matching
January 20, 2019 - Study implicates hyperactive immune system in aging brain disorders
January 20, 2019 - Cancer Diagnosis May Quadruple Suicide Risk
January 20, 2019 - Parkinson’s disease experts devise a roadmap
January 20, 2019 - Research brings new hope to treating degenerative brain diseases
January 20, 2019 - Scientists pinpoint a set of molecules that wire the body weight center of the brain
January 20, 2019 - Researchers get close to developing elusive blood test for Alzheimer’s disease
January 20, 2019 - UCLA researchers demonstrate new technique to develop cancer-fighting T cells
January 20, 2019 - Researchers discover how cancer cells avoid genetic meltdown
January 20, 2019 - Exercise makes even the ‘still overweight’ healthier: study
January 20, 2019 - University of Utah to establish first-of-its-kind dark sky studies minor in the US
January 20, 2019 - School-based nutritional programs reduce student obesity
January 20, 2019 - Improved maternity care practices in the southern U.S. reduce racial inequities in breastfeeding
January 20, 2019 - New enzyme biomarker test indicates diseases and bacterial contamination
January 20, 2019 - Republican and Democratic governors have different visions to transform health care, say researchers
January 20, 2019 - Researchers discover that spin flips happen in only half a picosecond in the course of a chemical reaction
January 20, 2019 - Suicide Risk Up More Than Fourfold for Cancer Patients
January 20, 2019 - Doctors find 122 nails in Ethiopian’s stomach
January 20, 2019 - UV disinfection technology eliminates up to 97.7% of pathogens in operating rooms
January 20, 2019 - Researchers discover mechanism which drives leukemia cell growth
January 20, 2019 - AHA: Infection as a Baby Led to Heart Valve Surgery for Teen
January 20, 2019 - Injection improves vision in a form of childhood blindness
January 20, 2019 - Multiple sclerosis therapies delay progression of disability
January 20, 2019 - New study finds infrequent helmet use among bike share riders
January 20, 2019 - Clearing up information about corneal dystrophies
January 20, 2019 - Researchers describe new behavior in energy metabolism that refutes existing evidence
January 20, 2019 - New study takes first step toward treating endometriosis
January 20, 2019 - Researchers find how GREB1 gene promotes resistance to prostate cancer treatments
January 20, 2019 - Replacing Sitting Time With Activity Lowers Mortality Risk
January 20, 2019 - A simple, inexpensive intervention makes birth safer for moms and babies in parts of Africa
January 19, 2019 - New anti-inflammatory compound acts as ‘surge protector’ to reduce cancer growth
January 19, 2019 - Significant flaws found in recently released forensic software
January 19, 2019 - New Leash on Life? Staying Slim Keeps Pooches Happy, Healthy
January 19, 2019 - Men and women remember pain differently
January 19, 2019 - Rising air pollution linked with increased ER visits for breathing problems
January 19, 2019 - Study uses local data to model food consumption patterns among Seattle residents
January 19, 2019 - The brain’s cerebellum plays role in controlling reward and social behaviors, study shows
January 19, 2019 - Relationship between nurse work environment and patient safety
January 19, 2019 - Pioneering surgery restores movement to children paralyzed by acute flaccid myelitis
January 19, 2019 - Genetic variants linked with risk tolerance and risky behaviors
January 19, 2019 - New research provides better understanding of our early human ancestors
January 19, 2019 - First-ever tailored reporting guidance to improve patient care and outcomes
January 19, 2019 - 4.6 percent of Massachusetts residents have opioid use disorder
January 19, 2019 - New study suggests vital exhaustion as risk factor for dementia
January 19, 2019 - New antibiotic discovery heralds breakthrough in the fight against drug-resistant bacteria
January 19, 2019 - Ural Federal University scientists synthesize a group of multi-purpose fluorophores
January 19, 2019 - Researchers identify new therapeutic target in the fight against chronic liver diseases
January 19, 2019 - Preparation, characterization of Soyasapogenol B loaded onto functionalized MWCNTs
January 19, 2019 - FDA Approves Ontruzant (trastuzumab-dttb), a Biosimilar to Herceptin
January 19, 2019 - Tobacco use linked with higher use of opioids and sedatives
January 19, 2019 - Study delves deeper into developmental dyslexia
January 19, 2019 - Anti-vaccination movement one of the top health threats in 2019 says WHO
January 19, 2019 - Newly developed risk score more effective at identifying type 1 diabetes
January 19, 2019 - Highly effective protocol to prepare cannabis samples for THC/CBD analysis
January 19, 2019 - Prinston Pharmaceutical Inc. Issues Voluntary Nationwide Recall of Irbesartan and Irbesartan HCTZ Tablets Due to Detection of a Trace Amount of Unexpected Impurity, N-Nitrosodiethylamine (NDEA) in the Products
January 19, 2019 - How does solid stress from brain tumors cause neuronal loss, neurologic dysfunction?
January 19, 2019 - $14.7 million partnership to supercharge vaccine development
January 19, 2019 - Ian Fotheringham receives Charles Tennant Memorial Lecture award
January 19, 2019 - Brain vital signs detect neurophysiological impairments in players with concussions
January 19, 2019 - Lack of job and poor housing conditions increased likelihood of people attending A&E
January 19, 2019 - Novel targeted drug delivery system improves conventional cancer treatments
January 19, 2019 - Rutgers study finds gene responsible for spread of prostate cancer
January 19, 2019 - Complications Higher Than Expected for Invasive Lung Tests
January 19, 2019 - 3-D printed implant promotes nerve cell growth to treat spinal cord injury
January 19, 2019 - Automated texts lead to improved outcomes after total knee or hip replacement surgery
January 19, 2019 - Poor cardiorespiratory fitness could increase risk of future heart attack, finds new study
January 19, 2019 - Drinking soft drinks while exercising in hot weather may increase risk of kidney disease
January 19, 2019 - Formlabs 3D prints anatomical models
January 19, 2019 - Heart-Healthy Living Also Wards Off Type 2 Diabetes
January 19, 2019 - Teaching Kids to Be Smart About Social Media (for Parents)
January 19, 2019 - Metabolite produced by gut microbiota from pomegranates reduces inflammatory bowel disease
January 19, 2019 - Researchers examine how spray from showers and toilets expose us to disease causing bacteria
January 19, 2019 - Behavioral experiments confirm that additional neurons improve brain function
January 19, 2019 - New study compares performance of real-time infectious disease forecasting models
January 19, 2019 - Obesity can be risk factor for developing renal cell carcinoma, confirms study
January 19, 2019 - New regulation designs on cigarette packs direct smokers’ attention to health warnings
January 19, 2019 - QIAGEN receives first companion diagnostic approval in Japan
January 19, 2019 - Study explores role of Dunning-Kruger effect in anti-vaccine attitudes
January 19, 2019 - Hepatitis C-infected patients with a history of liver cancer can be treated with antivirals
January 19, 2019 - Study shows how gut bacteria affect the treatment of Parkinson’s disease
Scientists use CRISPR tool to make multiple edits to DNA samples ‘in vitro’

Scientists use CRISPR tool to make multiple edits to DNA samples ‘in vitro’

image_pdfDownload PDFimage_print

Delaware’s Gene Editing Institute Discovery Could Rapidly Advance Personalized Cancer Care

Scientists at Christiana Care Health System’s Gene Editing Institute have developed a potentially breakthrough CRISPR gene-editing tool. It could allow researchers to take fragments of DNA extracted from human cells, put them into a test tube, and quickly and precisely engineer multiple changes to the genetic code, according to a new study published today in the CRISPR Journal.

Investigators at the Gene Editing Institute, which is part of the Helen F. Graham Cancer Center & Research Institute at Christiana Care, said their new “cell-free” CRISPR technology is the first CRISPR tool capable of making multiple edits to DNA samples “in vitro,” which means in a test tube or petri dish. The advance could have immediate value as a diagnostic tool, replicating the exact genetic mutations found in the tumors of individual cancer patients. Mutations that cause cancer to spread can differ from patient to patient, and being able to quickly identify the correct mutation affecting an individual patient can allow clinicians to implement a more targeted treatment strategy.

“With this new advance, we should be able to work with laboratory cultures and accomplish gene edits in less than a day, significantly reducing the time required for diagnostics compared to other CRISPR tools, and with much greater precision,” said Eric Kmiec, Ph.D., director of the Gene Editing Institute and principal author of the study. “This is particularly important for diagnostics linked to cancer care where time is critical.”

Kmiec also said that while other CRISPR tools are restricted to editing or repairing short segments of DNA code within a single gene, his team’s new CRISPR tool could lead to applications that are capable of removing and replacing entire genes. This could be important, he said, for using CRISPR to treat disease. Kmiec noted that while some ailments, like sickle cell anemia and Huntington’s disease, involve faulty DNA within a single gene, others, like Alzheimer’s and heart disease, appear to involve malfunctions in multiple genes where the best option “is not really gene editing, but gene replacement.”

CRISPR stands for “clustered regularly interspaced short palindromic repeats.” It is a defense mechanism found in bacteria that allows the bacteria to recognize and slice up the DNA of invading viruses. Scientists have learned how to manipulate this mechanism so that it essentially can be programmed to find and remove a specific sequence of DNA code-;which acts like software for controlling genes-;and replace it with a different sequence. This capability has generated unprecedented excitement about developing different CRISPR tools that could produce breakthrough treatments for a wide range of diseases by repairing a damaged gene, modifying it or deleting it entirely.

In the study published today, Kmiec and his colleagues-;lead author Brett Sansbury and co-author Amanda Wagner-;describe developing a “cell-free” CRISPR tool that can modify genes contained in something called a DNA plasmid. A plasmid is a type of DNA molecule that can be removed from a cell and maintained and manipulated in a petri dish or test tube.

The study notes that a key feature of the new CRISPR tool is that it uses a protein called Cpf1, more recently referred to as Cas12a, to essentially function like scissors for cutting out and inserting a targeted line of genetic code. Most of the CRISPR work underway today employs a different “set of scissors” in the form of an enzyme called Cas9. However, Sansbury said while the CRISPR-Cas9 gene editing system has proven to be effective at modifying genes that are inside a cell, it performed poorly when her team tried to use it in a “cell-free” environment to quickly engineer complex changes to DNA plasmids.

“It could be that there is something within the very complex machinery of a cell that allows the Cas9 enzyme to more easily accomplish deletions and insertions,” Sansbury said. “But it performed very poorly in our cell-free extracts.”

Sansbury noted that when Cas9 cuts DNA, the result can be “blunt ends,” while Cpf1 produces “sticky ends.” She said that the blunt-ended outcome could impede the ability to process the cut ends, which allows for the removal or “resection” of a section of genetic code and then seamlessly insert and attach new code.

Bringing the CRISPR Revolution to Everyday Cancer Care

The Gene Editing Institute is now working to use the new CRISPR-Cpf1 breakthrough to provide something akin to CRISPR on a computer chip to a commercial partner involved in cancer diagnostics that is intended to drive personalized cancer care.

“The speed at which you see our discovery moving from the bench to the bedside is unprecedented but not unanticipated,” said Nicholas Petrelli, M.D., FACS, Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute at Christiana Care. “The Gene Editing Institute exists within a community hospital system where we are committed to a patient-first approach to biomedical research. This major advance in CRISPR-assisted gene editing was accomplished with the support from the BIRD Foundation, which wants to see a commercial partner on board from the beginning to ensure that any discoveries will quickly benefit patients.”

Sansbury and Kmiec said that while their work with their CRISPR-Cpf1tool has confirmed its usefulness for reliably editing DNA samples that are part of a diagnostic test, it is not yet fully developed as a therapeutic tool for directly treating disorders that would involve repairing or removing malfunctioning genes in humans, animals or plants. However, by allowing gene editing to be quickly and precisely accomplished in a test tube or petri dish, they believe their tool is ideal for revealing more about how CRISPR actually modifies the genome, a process that remains largely shrouded in mystery.

“When you’re working with CRISPR inside a cell, you’re kind of working in a black box where you can’t really observe the gears of the machinery that are doing these amazing things,” Kmiec said. “You can see the results, the edits to the genes, but not necessarily how you got there, which is important for ensuring that CRISPR can be safely used to treat patients.”

“The Gene Editing Institute’s cell-free CRISPR-Cpf1 system is yet another landmark CRISPR-related discovery to emerge from Christiana Care Health System,” Janice E. Nevin, M.D., MPH, Christiana Care president and chief executive officer, said.

In 2016, scientists at the Gene Editing Institute described in the journal, Scientific Reports, how they combined CRISPR with short strands of synthetic DNA to greatly enhance the precision and reliability of the CRISPR gene editing technique. Called excision and corrective therapy, or EXACT, this new tool acts as both a template and a bandage for repairing a malfunctioning gene.

Source:

https://christianacare.org/

Tagged with:

About author

Related Articles