Breaking News
August 16, 2018 - Ablating the mutant p53 gene in mice with colorectal cancer inhibits tumor growth
August 16, 2018 - Higher BMI in people with prediabetes related to evening preference and lack of sufficient sleep
August 16, 2018 - Using peripheral nerve blocks to treat facial pain may produce long-term pain relief
August 16, 2018 - Neural stem cells are the key to tail regeneration
August 16, 2018 - Study compares genetic and neural contributions to ADHD in children with or without TBI
August 16, 2018 - Adding energy drinks to alcohol may exacerbate negative effects of binge drinking
August 16, 2018 - Eye Examination Can Help Detect Abuse in Children
August 16, 2018 - Know the Difference: Rheumatoid Arthritis or Osteoarthritis?
August 16, 2018 - From ‘sea of mutations,’ two possible cancer links rise to the surface
August 16, 2018 - Does medical school take too long?
August 16, 2018 - Brown University researchers reveal key physical properties of ‘giant’ cancer cells
August 16, 2018 - Regular resistance training improves exercise motivation
August 16, 2018 - Feds urge states to encourage cheaper plans off the exchanges
August 16, 2018 - Seven activities that prevent you from getting quality sleep during summer
August 16, 2018 - Five ways to tell if your baby is getting enough milk from breastfeeding
August 16, 2018 - From Pigs to Peacocks, What’s Up With Those ‘Emotional-Support Animals’?
August 16, 2018 - Breast cancers enlist the help of normal cells to help them spread and survive
August 16, 2018 - Engaging with “high-need” patients outside the clinic
August 16, 2018 - Research illuminates how online forum may offer suicide prevention support for males
August 16, 2018 - Researchers identify way to grow immune cells at large scale for preventing cancer reoccurrence
August 15, 2018 - Keck Medicine of USC’s hospitals ranked among nation’s best for the 10th consecutive year
August 15, 2018 - Researchers compare existing approaches for automating diagnostic procedures of skin lesions
August 15, 2018 - Autism risk determined by health of mom’s gut, research reveals
August 15, 2018 - WELL for Life challenges you to explore the great outdoors
August 15, 2018 - ‘Zombie’ gene protects elephants from cancer, study finds
August 15, 2018 - Ebola outbreak in Congo spreads to active combat zone
August 15, 2018 - Study highlights pollution exposure of babies in prams
August 15, 2018 - Study provides insight into link between sleep apnea and lipid metabolism
August 15, 2018 - New study focuses on promise of gene therapy for Amish nemaline myopathy
August 15, 2018 - Researchers discover new approach to alleviate chronic itch
August 15, 2018 - Uncovering the Mysteries of MS: Medical Imaging Helps NIH Researchers Understand the Tricky Disease
August 15, 2018 - Autistic people at greater risk of becoming homeless – new research
August 15, 2018 - New imaging technique can spot tuberculosis infection in an hour
August 15, 2018 - Scientists study effects of eating breakfast versus fasting overnight before exercise
August 15, 2018 - Talking with children about suicide could save lives
August 15, 2018 - Grip strength of children predicts future cardiometabolic health
August 15, 2018 - Innovative oncofertility program launched by RMA of New York and Mount Sinai Health System
August 15, 2018 - Study shows efficacy, safety of AAV5-based gene therapy to treat sheep model of achromatopsia
August 15, 2018 - Simple score helps predict which hospitalized heart attack patients are at high risk of readmissions
August 15, 2018 - New discoveries show how protein droplets do more than keep cells’ interiors tidy
August 15, 2018 - Study shows impact of optimizing airport flight patterns on human health
August 15, 2018 - Life experiences of feeling unwanted or unplanned associated with attachment insecurity
August 15, 2018 - ACS Briefing Discusses Use of Lessons From Combat Care
August 15, 2018 - Study identifies distinct origin of ADHD in children with history of brain injury
August 15, 2018 - IgG3 antibody stops B cells from fighting pathogens in HIV patients
August 15, 2018 - Scientists discover key vulnerability of mixed lineage leukemia
August 15, 2018 - College students may experience pressures from secondary exposure to opioid abuse
August 15, 2018 - Powerful new microscope reveals inner workings of human cells with unprecedented clarity
August 15, 2018 - Married people who fight nastily more likely to suffer from leaky guts, study suggests
August 15, 2018 - Working Out After Baby – Drugs.com MedNews
August 15, 2018 - Rheumatoid Factor (RF) Test: MedlinePlus Lab Test Information
August 15, 2018 - ADHD linked to an increased risk of injury in children, study finds
August 15, 2018 - UIC researchers receive NIH funding to develop a better way to regenerate bone or tissues
August 15, 2018 - Study reveals how immune cells in the brain influence sexual behavior
August 15, 2018 - Researchers move closer to finding potential soft spot in drug-resistant tuberculosis
August 15, 2018 - Real-time dynamic monitoring of cell’s nucleus for effective cancer screening
August 15, 2018 - Lower rates of Medicare preventive care visits found in racial, ethnic minority older adults
August 15, 2018 - Scientists identify stress hormone as key factor in failure of immune system to inhibit leukemia
August 15, 2018 - Cytoplan introduces three new nutritional supplements
August 15, 2018 - Effective hemorrhage control critical for survival after motorsport accidents
August 15, 2018 - Sygnature Discovery announces ambitious expansion plan with addition of Alderley Park facility
August 15, 2018 - Dietary carbohydrates could lead to osteoarthritis, new study finds
August 15, 2018 - Male tobacco smokers have decreased number of cannabinoid CB1 receptors, study reveals
August 15, 2018 - Scientists explore ways for drug therapies to reach deadly brain tumors
August 15, 2018 - Rethinking fundamental rule of stroke care: ‘Time is brain!’
August 15, 2018 - Scientists reveal role of ‘junk DNA’ in cancer dissemination
August 15, 2018 - Google’s DeepMind AI could soon be diagnosing eye conditions
August 15, 2018 - Scientists trick the brain to embody the prosthetic limb
August 15, 2018 - Researchers focus on uncoupling obesity from diabetes
August 15, 2018 - Clinical study shows how EarlySense system effectively detects opioid-induced respiratory depression
August 15, 2018 - A class of proteins shown to be effective in reducing drug-seeking behaviors
August 15, 2018 - FundamentalVR launches first-of-its-kind SaaS software platform for surgical simulation
August 15, 2018 - Gemphire Announces Termination of Phase 2a Clinical Trial of Gemcabene in Pediatric NAFLD
August 15, 2018 - Rheumatoid arthritis in pregnancy associated with low birth weight and premature birth
August 15, 2018 - Study may help increase effectiveness of antibiotics against drug-resistant bacteria
August 15, 2018 - Analyzing resident-to-resident incidents in dementia may hold the key to reducing future fatalities
August 15, 2018 - Robotic walking frame aims to help maintain mobility of older adults
August 15, 2018 - Simple intervention during routine care reduces alcohol consumption in men with HIV
August 15, 2018 - Genetics Home Reference: gout
August 15, 2018 - Scientists ID genesis of disease, focus efforts on shape-shifting tau
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