Breaking News
December 17, 2018 - CTF along with NTAP and Sage announce first-ever open data portal for neurofibromatosis
December 17, 2018 - Intimacy: The Elusive Fountain of Youth?
December 17, 2018 - Will saliva translate to a real diagnostic tool?
December 17, 2018 - DFG establishes nine new Research Units and one new Clinical Research Unit
December 17, 2018 - Assisted living’s breakneck growth leaves patient safety behind
December 17, 2018 - America’s teens report dramatic increase in their use of vaping devices in just one year
December 17, 2018 - Enlarged heart linked to a higher risk of dementia
December 17, 2018 - Prostate cancer detection using MRI now first-line investigation tool
December 17, 2018 - Adolescents who use cognitive reappraisal had better metabolic measures, shows study
December 17, 2018 - Probiotics may offer therapeutic benefits for biopolar patients
December 17, 2018 - Stealth BioTherapeutics Granted Fast Track Designation for Elamipretide for the Treatment of Dry Age-Related Macular Degeneration with Geographic Atrophy
December 17, 2018 - Studies reveal role of red meat in gut bacteria, heart disease development
December 17, 2018 - Eisai enters into agreement with Eurofarma for its anti-obesity agent lorcaserin
December 17, 2018 - Researchers use brain connectome to reassess neuroimaging findings of Alzheimer’s disease
December 17, 2018 - “Miracle” baby survives Ebola in Congo and rapid a new Ebola detection device
December 17, 2018 - Mechanisms behind neonatal diabetes uncovered
December 17, 2018 - AHF urges the WHO to expedite approval process for vaccine effective against Ebola
December 17, 2018 - Study finds misuse of benzodiazepines to be highest among young adults
December 17, 2018 - TGen receives PayPal grant to underwrite costs of genetic tests for children with rare disorders
December 17, 2018 - New research highlights why HIV-infected patients suffer higher rates of cancer
December 17, 2018 - Antibiotic-resistant bacteria could soon be targeted with Alzheimer’s drug
December 17, 2018 - Rutgers scientists take an important step in making diseased hearts heal themselves
December 17, 2018 - Tailored Feedback at CRC Screen Improves Lifestyle Behaviors
December 17, 2018 - Loss of two genes drives a deadly form of colorectal cancer, reveals a potential treatment
December 17, 2018 - How the Mediterranean Diet Can Help Women’s Hearts
December 17, 2018 - Sustained connections associated with symptoms of autism
December 17, 2018 - Concussion rates among young football players were higher than previously reported
December 17, 2018 - Cresco Labs granted approval to operate marijuana dispensary in Ohio
December 17, 2018 - Study provides insight into health risks facing new mothers
December 17, 2018 - AMSBIO expands Wnt signaling pathway product range to aid research
December 16, 2018 - Surgical treatment unnecessary for many prostate cancer patients
December 16, 2018 - Excess weight responsible for cancers globally finds report
December 16, 2018 - Regular sex associated with greater enjoyment of life in seniors
December 16, 2018 - Social stigma contributes to poor mental health in the autistic community
December 16, 2018 - Multidisciplinary team successfully performs complex surgery on patient suffering from enlarged skull
December 16, 2018 - Experts analyze data that can guide antidepressant discontinuation
December 16, 2018 - Menlo Therapeutics’ Successful Phase 2 Clinical Trial of Serlopitant Demonstrates Reduction of Pruritus Associated with Psoriasis
December 16, 2018 - Siblings of children with autism or ADHD are at elevated risk for both disorders
December 16, 2018 - New project aims to understand why and how metabolic disorders develop in patients
December 16, 2018 - Diets containing GM maize have no harmful effects on health or metabolism of rats
December 16, 2018 - Are doctors and teachers confusing immaturity and attention deficit?
December 16, 2018 - Hearing loss linked with increased risk for premature death
December 16, 2018 - Chromatrap buffer reagents for lysing cells offer many benefits
December 16, 2018 - Young Breast Cancer Patients Face Higher Risk for Osteoporosis
December 16, 2018 - 3-D printing offers helping hand to people with arthritis
December 16, 2018 - Community Health Choice helps manage complex and chronic care conditions
December 16, 2018 - Regular trips out could dramatically reduce depression in older age
December 16, 2018 - CWRU to use VivaLNK’s Vital Scout device for stress study in student athletes
December 16, 2018 - ‘Easy Way Out’? Stigma May Keep Many From Weight Loss Surgery
December 16, 2018 - Gout drug may protect against chronic kidney disease
December 16, 2018 - Talking about memories enhances the wellbeing of older and younger people
December 16, 2018 - Occupational exposure to pesticides increases risk for cardiovascular disease among Latinos
December 16, 2018 - A biomarker in the brain’s circulation system may be Alzheimer’s earliest warning
December 16, 2018 - Magnesium may play important role in optimizing vitamin D levels, study shows
December 16, 2018 - The effect of probiotics on intestinal flora of premature babies
December 16, 2018 - Parents spend more time talking with kids about mechanics of using mobile devices
December 16, 2018 - Biohaven Announces Positive Results from Ongoing Rimegepant Long-Term Safety Study
December 16, 2018 - Arterial stiffness may predict dementia risk
December 16, 2018 - Study explores link between work stress and increased cancer risk
December 16, 2018 - Sex work criminalization linked to incidences of violence finds study
December 16, 2018 - Johns Hopkins researchers discover swarming behavior in fish-dwelling parasite
December 16, 2018 - Schistosomiasis prevention and treatment could help control HIV
December 16, 2018 - Early postpartum opioids linked with persistent usage
December 16, 2018 - Johns Hopkins researchers identify molecular causes of necrotizing enterocolitis in preemies
December 16, 2018 - Advanced illumination expands capabilities of light-sheet microscopy
December 16, 2018 - Alzheimer’s could possibly be spread via contaminated neurosurgery
December 16, 2018 - Unraveling the complexity of cancer biology can prompt new avenues for drug development
December 16, 2018 - Inflammatory Bowel Disease, Prostate Cancer Linked
December 16, 2018 - Cannabis youth prevention strategy should target mental wellbeing
December 15, 2018 - Recent developments and challenges in hMAT inhibitors
December 15, 2018 - Sewage bacteria found lurking in Hudson River sediments
December 15, 2018 - CDC selects UMass Amherst biostatistician model that helps predict influenza outbreaks
December 15, 2018 - Researchers reveal brain mechanism that drives itch-evoked scratching behavior
December 15, 2018 - New computer model helps predict course of the disease in prostate cancer patients
December 15, 2018 - Obesity to Blame for Almost 1 in 25 Cancers Worldwide
December 15, 2018 - How the brain tells you to scratch that itch
December 15, 2018 - New findings could help develop new immunotherapies against cancer
December 15, 2018 - World’s largest AI-powered medical research network launched by OWKIN
December 15, 2018 - Young people suffering chronic pain battle isolation and stigma as they struggle to forge their identities
December 15, 2018 - Lifespan extension at low temperatures depends on individual’s genes, study shows
Research team awarded $3.6 million to assess safety of genome editing

Research team awarded $3.6 million to assess safety of genome editing

image_pdfDownload PDFimage_print

As genome editing technologies quickly advance toward clinical therapies, they are raising hopes of a completely new way to treat disease. They are also bringing to light a number of challenges that need to be addressed before potential treatments can be widely used in patients.

To tackle these challenges and fuel efforts across the country, the National Institutes of Health (NIH) launched the Somatic Cell Genome Editing program. Among the program’s first grant recipients is a group led by Todd McDevitt, PhD, senior investigator at the Gladstone Institutes. The team was awarded more than $3.6 million over the next 5 years to assess the safety of genome editing in human cells and tissues.

Jennifer Doudna, PhD, a senior investigator at Gladstone and a professor at UC Berkeley, also received funding to expand the current toolkit for human genome editing by exploring new CRISPR-Cas proteins and enzymes that can repair DNA.

“This program is funded by the NIH’s Common Fund, indicating the importance–and promise–of genome editing technology, such as CRISPR-Cas9,” said Deepak Srivastava, MD, president of the Gladstone Institutes. “We are proud that Gladstone investigators are in a position to have a significant impact on shaping this field and its future clinical applications.”

For his project, bioengineering expert McDevitt has joined forces with another senior investigator at Gladstone, Bruce Conklin, MD, who is pioneering an approach called “genome surgery,” which reflects the precision of customizing genome therapies to individual patients.

Together, they assembled a team of leading investigators with complementary experience in tissue engineering, genome editing, gene therapy, stem cell biology, and single cell genomics. Their collaborators include Andrew May, DPhil, from the Chan Zuckerberg Biohub, as well as Luke Judge, MD, PhD, and Nicole Paulk, PhD, from UC San Francisco (UCSF).

“Our primary objective is to develop platforms that can accurately detect adverse effects of genome editing on physiological function,” said McDevitt, who is also a professor in the Department of Bioengineering and Therapeutic Sciences at UCSF. “By evaluating possible safety and toxicity issues in human cells and tissues, we hope to help avoid unanticipated effects in future clinical trials.”

Genome editing consists of making changes to a person’s DNA to remove, insert, or replace certain genes. So far, researchers have focused on exploring whether these edits are being made in the correct genes and whether other parts of the DNA are unintentionally affected.

The new project proposed by McDevitt’s group will expand current knowledge by also examining whether genome editing could lead to unexpected changes in the function of cells or tissues. More precisely, they will study the extent of DNA damage that can be tolerated before causing adverse functional consequences.

To do so, they will combine state-of-the-art methods for engineering human microtissues from stem cells with novel approaches for inducing precise genome edits and detecting any detrimental DNA damage.

McDevitt will leverage his laboratory’s expertise in developing human microtissues that faithfully mimic the way different cell types are organized and function as complex tissues. These models will serve as an ideal platform to identify and quantify adverse outcomes in response to genome editing.

“With the 3D environment of microtissues, we can study how cells cooperate and determine whether edits to one cell cause unpredicted consequences to adjacent cells,” explained McDevitt. “As a result, these tissues can be much more predictive of physiological effects than single cells grown in a dish.”

The research group will test different editing methods in heart, brain, and liver microtissues, given that all three of these tissues have relevant disease applications. For instance, many forms of heart disease and neurodegenerative diseases are caused by genetic mutations that could potentially be treated with genome editing.

“Microtissues provide an essential test prior to any human trial,” said Conklin, who is also a professor the Departments of Medical Genetics and Molecular Pharmacology at UCSF. “Since animal models are often poor predictors of activity in humans, few methods exist to determine both intended and unintended consequences of therapeutic interventions. Microtissues, however, will help predict the exact type of genome editing event that could be toxic to aide in the design and monitoring of safer clinical trials.”

For the first 3 years of the study, the research team will develop methods to detect the frequency and types of off-target genome edits that occur and correspond to specific adverse outcomes in live human cells and tissues. Then, they will use their systems to test new genome editors developed by other members of the Somatic Cell Genome Editing program to further refine and optimize their approach.

Ultimately, McDevitt, Conklin, and their collaborators will share their models for widespread use by other program members. In doing do, they hope to provide the scientific community with a critical new platform to assess both the safety and effectiveness of genome editing therapies before they are routinely tested in clinical medicine.

Source:

https://gladstone.org/about-us/press-releases/36-million-study-adverse-effects-genome-editing

Tagged with:

About author

Related Articles