- Press Release Distribution

Large NIH grant supports CRISPR-based gene therapy development for brain diseases

( A two-phase NIH grant will fund research into a new CRISPR-based gene therapy platform that will target genetic brain diseases like Angelman syndrome and H1-4 (HIST1H1E) syndrome.

A roughly $40 million National Institutes of Health (NIH) grant awarded to Yale School of Medicine will support the development of a gene-editing platform technology capable of reaching the human brain. The innovative new genome-editing technology, which was developed from the first phase from NIH Common Fund Somatic Cell Genome Editing (SCGE) program, could potentially lead to treatments or cures for many neurogenetic diseases.

Neurogenetic disorders can be devastating, and treatments are scarce. The two-phase grant from the NIH will support research into a novel CRISPR-based gene editing technology and delivery platform for targeting neurogenetic diseases. The grant will focus on Angelman syndrome and H1-4 syndrome as a proof-of-concept, and could be applicable to many neurogenetic disorders. The new delivery technology, known as STEP (Stimuli-responsive Traceless Engineering Platform), has the capacity to revolutionize genome-editing therapy and create a one-time treatment for a range of genetic disorders.

The work will be led by Yong-Hui Jiang, MD, PhD, professor of genetics, of pediatrics and of neuroscience and chief of medical genetics, and Jiangbing Zhou, PhD, professor of neurosurgery and of biomedical engineering, both at Yale School of Medicine. The team also includes co-leader Elizabeth Berry-Kravis, MD, PhD, professor of pediatrics and neurological sciences and director of the RUSH Pediatric Neurosciences F.A.S.T. Center for Translational Research at RUSH University in Chicago; and Allyson Berent, DVM, DACVIM and Jennifer Panagoulias of the Foundation for Angelman Syndrome Therapeutics (FAST). The HIST1H1E foundation led by Kimberly Greenberg will also participate the study. The first $26.5 million grant will support pre-clinical and toxicology studies in animal models and human brain organoids. If the milestones of the first phase are met, the NIH will provide an additional $13 million to fund clinical trials in humans.

“If we can prove the concept of this technology in the two diseases we’re studying, we can then apply it to hundreds or thousands of diseases of the brain,” says Jiang.

Existing Gene Therapy Methods Face Limitations

Until now, the development of gene therapy technologies has been slow as researchers focus on one disease at a time. Furthermore, existing gene therapies commonly rely on viruses as the delivery vehicle, but this method has risks. The exposure of the body to viral proteins can trigger adverse reactions. Viruses can incorporate DNA into the human genome and increase risk for tumor development. Viruses may be particularly not ideal for delivery of genome editing therapy due to a risk of off-target effects associated with long term gene expression.  While non-viral nanoparticle-based delivery platforms for genome editing options do exist, their delivery to the brain has been challenging due to many limitations.

New Platform Utilizes Ribonucleoproteins (RNPs) That Directly Access Brain

At Yale, a joint team led by Jiang and Zhou invented the STEP technology and successfully applied it for delivery of genome editing therapy for treatment of various diseases in animal models. Instead of viruses, the novel platform utilizes a chemical engineering approach to achieve brain-wide delivery of gene-editing with high efficiency.

“Over the past few years, we have been working on development of this technology. I am thrilled about the opportunity to bring it to the clinical bedside,” says Zhou.

Through this new system, the team administers the delivery technology intrathecally, or through a spinal tap. Due to their unique physical chemical properties, STEP-RNPs demonstrate a great ability to penetrate the brain and edit neuronal cells with high efficiency. After entering the cells, RNPs are quickly degraded, limiting the risk of off-target effects.

Other molecular therapies such as antisense oligonucleotides (ASOs) require frequent treatments, but this new technology could work as a single dose with a permanent effect and potentially with a greater efficiency than ASOs.

A Potential Therapeutic Platform for a Range of Brain Diseases

The team will be focused on Angelman syndrome and H1-4 syndrome because prior research already indicates significant promise of the benefits of gene-editing therapy in treating these conditions. But ideally, their strategy can be adopted for treating many other neurogenetic disorders as well. In particular, some neurogenetic conditions are rare diseases, so there is often little incentive for pharmaceutical companies to invest in therapeutics. The researchers hope their platform will increase these companies’ interest in investing because it can be applied to many different diseases.

In May, Yale School of Medicine joined the NORD Rare Disease Centers of Excellence network. This work adds to a growing concentration of groundbreaking basic research, clinical translation, and clinical care in the rare disease space taking place at the Yale School of Medicine.

Other faculty participants for the projects from Yale school of medicine include James McPartland, PhD; Julie Wolf, PhD; Michele Spencer-Manzon, MD; Hui Zhang, MD, PhD; Caroline Hendry, PhD; James Dziura, PhD, MPH; Nigel Bamford, MD; Kathleen Cardinale, MD; Caihong Qiu, PhD; and Eric Velazquez, MD. The NIH Federal Award Identification Number for the grant is UG3TR004713.



Bursts of star formation explain mysterious brightness at cosmic dawn

Bursts of star formation explain mysterious brightness at cosmic dawn
When scientists viewed the James Webb Space Telescope’s (JWST) first images of the universe’s earliest galaxies, they were shocked. The young galaxies appeared too bright, too massive and too mature to have formed so soon after the Big Bang. It would be like an infant growing into an adult within just a couple years. The startling discovery even caused some physicists to question the standard model of cosmology, wondering whether or not it should be upended. Using new simulations, a Northwestern University-led ...

Van Andel Institute scientist awarded $2.9 million to tackle insulin resistance, a driver of Type 2 diabetes

Van Andel Institute scientist awarded $2.9 million to tackle insulin resistance, a driver of Type 2 diabetes
Van Andel Institute’s Nick Burton, Ph.D., has earned a five-year, nearly $2.9 million New Innovator Award from the National Institutes of Health Common Fund to find new ways to fix or prevent insulin resistance, a key driver of Type 2 diabetes.   Although manageable with treatment, there currently is no way to repair the underlying mechanisms that cause the disease. Furthermore, it remains unclear why some people are more prone to Type 2 diabetes while others are resistant. To find a solution, Burton ...

SwRI study suggests large mound structures on Kuiper belt object Arrokoth may have common origin

SwRI study suggests large mound structures on Kuiper belt object Arrokoth may have common origin
SAN ANTONIO — October 3, 2023 —A new study led by Southwest Research Institute (SwRI) Planetary Scientist and Associate Vice President Dr. Alan Stern posits that the large, approximately 5-kilometer-long mounds that dominate the appearance of the larger lobe of the pristine Kuiper Belt object Arrokoth are similar enough to suggest a common origin. The SwRI study suggests that these “building blocks” could guide further work on planetesimal formational models. Stern presented these findings this week ...

Marine chemical biologist Mandë Holford wins prestigious National Institutes of Health Pioneer Award for Venom Research

Marine chemical biologist Mandë Holford wins prestigious National Institutes of Health Pioneer Award for Venom Research
NEW YORK, Oct. 3, 2023 — Mandë Holford, a professor in the Chemistry and Biochemistry departments at Hunter College and The City University of New York Graduate Center (CUNY Graduate Center), has won a National Institutes of Health Common Fund Pioneer Award for her trailblazing research exploring the therapeutic opportunities and properties of venoms from cephalopods and other marine mollusks. Holford received one of eight Pioneer Awards granted in 2023, which will total more than $47.7 million over five years. This is the first time a CUNY ...

Synthetic peptide could reduce vascular problems associated with COVID-ARDS

Synthetic peptide could reduce vascular problems associated with COVID-ARDS
AUGUSTA, Ga. (Oct. 4, 2022) – A synthetic peptide developed by researchers at the Medical College of Georgia could help reduce vascular problems associated with acute respiratory distress syndrome in COVID-19. In severe cases, COVID-19 is associated with the syndrome, which happens when fluid builds up in the tiny, elastic air sacs in the lungs, keeping them from filling with enough air and keeping oxygen from reaching the bloodstream. “These are the people who get the sickest from ...

Cardiology compensation and production remain relatively stable year-over-year

MedAxiom, the premier source for cardiovascular organizational performance solutions, has released its 2023 Cardiovascular Provider Compensation and Production Survey Report that includes data from the largest number of providers since its debut. The report features a foreword from MedAxiom President and CEO Jerry Blackwell, MD, MBA, FACC, on the consistency of year-over-year data from 2021 to 2022, the importance of a robust pool of data to form the foundation of the report, and the application of data as a strategic planning tool.  2023 Report Highlights:   Compensation and production ...

Optimizing continuous-variable functions with quantum annealing

Optimizing continuous-variable functions with quantum annealing
Quantum annealing (QA) is a cutting-edge algorithm that leverages the unique properties of quantum computing to tackle complex combinatorial optimization problems (a class of mathematical problems dealing with discrete-variable functions). Quantum computers use the rules of quantum physics to solve such problems potentially faster than classical computers. In essence, they can explore multiple solutions to a problem simultaneously, giving them a significant speed advantage for certain tasks over classical computers. In particular, QA harnesses the phenomenon of “quantum ...

City of Hope opens first U.S. multicenter clinical trial for robotic single-port mastectomies for breast cancer patients

LOS ANGELES — City of Hope, one of the largest cancer research and treatment organizations in the United States, is opening a multicenter clinical trial to evaluate the efficacy of robotic-assisted, single-incision mastectomies. The minimally invasive procedure, which preserves the nipple and leaves only a small hidden scar on the side of the body, could potentially lead to significant improvements for breast surgery. “City of Hope is once again taking the lead in investigating innovations, treatments and therapies that are making big leaps forward for patients with cancer. We’re participating ...

Emerging drug discovery ecosystems in Virginia

Emerging drug discovery ecosystems in Virginia
Oak Brook, IL – A Special Issue of SLAS Discovery, Emerging Drug Discovery Ecosystems, is new for September. Volume 28, Issue 6 features three perspectives, one original research article and one protocol that align with the Virginia Drug Discovery Consortium (VaDDC) and its efforts to enhance and promote drug discovery and development in the Commonwealth of Virginia. Perspective An acute respiratory distress syndrome drug development collaboration stimulated by the Virginia Drug Discovery Consortium This ...

Socioeconomic status and power outages

Socioeconomic status and power outages
Communities with more socioeconomic vulnerability experience longer-duration power outages than more advantaged communities, according to a study. Research has shown that environmental disasters hit economically and socially vulnerable communities hardest. Scott Ganz and colleagues assessed the unequal impacts caused by the procedures electric utilities follow to restore power to customers after extreme-weather related outages. Using data from eight Atlantic hurricanes that made landfall between January 2017 and October 2020, which knocked out power for a total of over 15 million customers in 588 counties in the Southeast, the authors find ...


Bioinformatics approach could help optimize soldiers’ training for improved readiness and recovery

Earth scientists describe a new kind of volcanic eruption

Warmer wetter climate predicted to bring societal and ecological impact to the Tibetan Plateau

Feeding infants peanut products protects against allergy into adolescence

Who will like beetle skewers? What Europeans think about alternative protein food

ETRI wins ‘iF Design Award’ for mobile collaborative robot

Combating carbon footprint: novel reactor system converts carbon dioxide into usable fuel

Investigating the origin of circatidal rhythms in freshwater snails

Altering cellular interactions around amyloid plaques may offer novel Alzheimer’s treatment strategies

Brain damage reveals part of the brain necessary for helping others

Surprising properties of elastic turbulence discovered

Study assesses cancer-related care at US hospitals predominantly serving minority populations compared with non-minority serving hospitals

First in-human investigator-initiated clinical trial to launch for refractory prostate cancer patients: Novel alpha therapy targets prostate-specific membrane antigen

Will generative AI change the way universities communicate?

Artificial Intelligence could help cure loneliness, says expert

Echidnapus identified from an ‘Age of Monotremes’

Semaglutide may protect kidney function in individuals with overweight or obesity and cardiovascular disease

New technique detects novel biomarkers for kidney diseases with nephrotic syndrome

Political elites take advantage of anti-partisan protests to disrupt politics

Tiny target discovered on RNA to short-circuit inflammation, UC Santa Cruz researchers find

Charge your laptop in a minute? Supercapacitors can help; new research offers clues

Scientists discover CO2 and CO ices in outskirts of solar system

Theory and experiment combine to shine a new light on proton spin

PKMYT1, a potential ‘Achilles heel’ of treatment resistant ER+ breast cancers with the poorest prognosis

PH-binding motifs as a platform for drug design: Lessons from protease-activated receptors (PARs)

Virginia Tech researcher creates new tool to move tiny bioparticles

On repeat: Biologists observe recurring evolutionary changes, over time, in stick insects

Understanding a broken heart

Genetic cause of rare childhood immune disorders discovered

With wobbling stars, astronomers gauge mass of 126 exoplanets and find 15 new ones

[] Large NIH grant supports CRISPR-based gene therapy development for brain diseases