Breaking News
November 21, 2018 - Smoke-free laws associated with reduced systolic blood pressure
November 21, 2018 - Achieving new guideline blood pressure goals may prevent 3 million cardiovascular events
November 21, 2018 - LDR brachytherapy for treating early-stage prostate cancer lacks conclusive data
November 21, 2018 - Purified omega-3 and aspirin reduce pre-cancerous bowel polyps, shows study
November 21, 2018 - Study warns that potential epigenetic therapy may boost lung cancer stem cells
November 21, 2018 - Noise pollution in hospital impact quality and safety of healthcare
November 21, 2018 - Higher Risk for Amputation, DKA With SGLT2 Inhibitors for T2DM
November 21, 2018 - Researchers stop ‘sneaky’ cancer cells in their tracks
November 21, 2018 - People who are afraid to draw their blood over-estimate the risk of fainting
November 21, 2018 - Personalized physical exercise reverses functional, cognitive deterioration in the elderly
November 21, 2018 - COPD linked to obesity in older women who have never smoked
November 21, 2018 - AHA: Cold-Weather Drinks Are Here, But Watch Out for the Calories
November 21, 2018 - Crowds line up at 1st East Coast pot shops
November 21, 2018 - Merck declares 2018 Life Science Award winners
November 21, 2018 - Many people underestimate the impact of sprains, say foot scientists
November 21, 2018 - Lower levels of protein make squamous carcinoma cells more invasive
November 21, 2018 - Study highlights a new predictor of type 2 diabetes
November 21, 2018 - NTU and TTSH join forces to improve doctor-patient communication
November 21, 2018 - New low-cost injectable hydrogel could help wounds heal faster
November 21, 2018 - Merck Announces Winners of 2018 Life Science Awards
November 21, 2018 - Check your medical records for dangerous errors
November 21, 2018 - Amount of weight regain after bariatric surgery helps predict health risks
November 21, 2018 - Heart failure patients with stronger hearts have more depressive symptoms, lower quality of life
November 21, 2018 - Women can be as resilient as men in undertaking arduous physical activity
November 21, 2018 - Receptor structure could be key to developing new osteoporosis drugs
November 21, 2018 - Researchers identify human white matter pathway associated with individual variability in human stereoacuity
November 21, 2018 - Vitamin D critical to early development of vertebrates, study suggests
November 21, 2018 - Myriad biological, societal factors that impact CKD severity for children of African descent
November 21, 2018 - Isofol Announces Initiation of a Pivotal Phase 3 Clinical Trial of arfolitixorin for the Treatment of Metastatic Colorectal Cancer
November 21, 2018 - Experts offer more clarity on managing common ankle fractures
November 21, 2018 - About 300 million bits of DNA are missing from basic reference genome, report scientists
November 21, 2018 - Study explores how the moving brain processes visual information
November 21, 2018 - Biomedical engineers stop cancer cells from moving and spreading
November 21, 2018 - Gut protein mutations protect against spikes in blood glucose levels
November 21, 2018 - First probabilistic atlas of thalamus nuclei to better understand the brain
November 21, 2018 - Peanut allergies could soon have a drug treatment
November 21, 2018 - Vanderbilt researchers isolate antibody that can neutralize West Nile virus
November 21, 2018 - KHN’s ‘What the Health?’ Health nerd books for the holidays
November 21, 2018 - MDMA could help gain trust but does not make one naive find researchers
November 21, 2018 - Study uncovers new mechanism controlling the master cancer regulator
November 21, 2018 - Online communication technologies could stave off depression among seniors, shows study
November 21, 2018 - FDA Approves Gamifant (emapalumab-lzsg) for Primary Hemophagocytic Lymphohistiocytosis
November 21, 2018 - Artificial intelligence predicts treatment effectiveness
November 21, 2018 - A bicyclist’s road to recovery after traumatic brain injury
November 21, 2018 - New research project to combat obesity, type 2 diabetes receives NIH funding
November 21, 2018 - Humans play key role in distribution and transmission of Bartonella bacteria
November 21, 2018 - First modeling system developed for testing age-specific human immune responses to vaccines
November 21, 2018 - FDA Alert: Gilenya (fingolimod): Drug Safety Communication
November 21, 2018 - Uric Acid Test: MedlinePlus Lab Test Information
November 21, 2018 - Researchers use genetics to predict response to antipsychotic medications
November 21, 2018 - Proposal to include the price of drugs in television ads is flawed, Stanford scholar writes
November 21, 2018 - Disrupting reproduction strategy of disease-causing parasites could help fight malaria
November 20, 2018 - ACAAI: Almost 2 Percent of Children Have Milk Allergy
November 20, 2018 - Congenital anomalies of kidney and urinary tract – Genetics Home Reference
November 20, 2018 - Can video games improve the health of older adults with schizophrenia?
November 20, 2018 - Can flicking a molecular switch restore the aging immune system’s competence?
November 20, 2018 - Restek launches new Oregon cannabis pesticide standards
November 20, 2018 - Health sector coalition urges Government to safeguard patients in future UK-EU relationship
November 20, 2018 - Study evaluates second-hand marijuana smoke exposure among children
November 20, 2018 - Scientists identify three genes responsible for recurrent molar pregnancies
November 20, 2018 - Researchers identify multisystem disorder caused by bi-allelic variants in CCDC47 gene
November 20, 2018 - Dining Out With Allergies Is Tough, But These Steps Can Help
November 20, 2018 - Breastfeeding protects infants from antibiotic-resistant bacteria
November 20, 2018 - AI matched, outperformed radiologists in screening X-rays for certain diseases | News Center
November 20, 2018 - Adolescents increasingly choose marijuana over cigarettes, alcohol
November 20, 2018 - World’s first medical imaging scanner produces diagnostic scan of the whole human body
November 20, 2018 - Cytocybernetics receives NIMH award to move into neuronal drug development
November 20, 2018 - Researchers discover new information on pathological mechanisms of Alzheimer’s disease
November 20, 2018 - ‘Unknown’ enzyme may be key to new treatment for inflammatory diseases
November 20, 2018 - Recreational drug may help people regain trust in others
November 20, 2018 - Researchers identify gene vital for post-stroke recovery
November 20, 2018 - Scientists identify novel target for neuron regeneration, functional recovery in spinal cord injury
November 20, 2018 - Potential new therapeutic approach developed for synovial sarcoma
November 20, 2018 - Skeletal imitation reveals how bones grow atom-by-atom
November 20, 2018 - Autism behaviors show unique brain network fingerprints in infants
November 20, 2018 - Location matters for inflammation clearance
November 20, 2018 - Towards finding a druggable cancer target
November 20, 2018 - Ultragenyx Announces Intent to Submit New Drug Application to U.S. FDA for UX007 for the Treatment of Long-chain Fatty Acid Oxidation Disorders in Mid-2019
November 20, 2018 - Cooling ‘brains on fire’ to treat Parkinson’s
November 20, 2018 - Less pollution could increase the average lifespan of Copenhageners by an entire year in 2040
Researchers use genome editing to reduce cholesterol levels in animal model

Researchers use genome editing to reduce cholesterol levels in animal model

image_pdfDownload PDFimage_print

Using genome editing to inactivate a protein called PCSK9 effectively reduces cholesterol levels in rhesus macaques, a species of monkey, according to researchers from the Perelman School of Medicine at the University of Pennsylvania. This is the first demonstration of a clinically relevant reduction of gene expression in a large animal model using genome editing. The team published their study this week in Nature Biotechnology, in which they describe a possible new approach for treating heart disease patients who do not tolerate PCSK9 inhibitors-;drugs that are commonly used to combat high cholesterol.

Normally, the PCSK9 protein prevents receptors from removing excess LDL (“bad” cholesterol) in the liver. In the clinic, it has also been shown that inhibiting PCSK9 can lower LDL in humans. However, some patients with hypercholesterolemia-;an extreme form of cardiovascular disease-;do not tolerate these drugs. This study suggests that genome editing shows promise as a therapeutic approach for these patients.

“Most often these patients are treated with repeated injections of an antibody to PCSK9,” said first author Lili Wang, PhD, a research associate professor in Medicine. “But, our study shows that with successful genome editing, patients who cannot tolerate inhibitor drugs might no longer need this type of repeat treatment.”

Coauthors at Precision Biosciences, a biotech firm in Durham, NC, engineered an enzyme called a meganuclease to specifically recognize and inactivate the PCSK9 gene. In this study, the scientists employed an adeno-associated virus (AAV) vector carrying the meganuclease to disrupt the PCSK9 gene in the primates’ liver.

In animals treated with middle- and high-dose AAV vectors, PCSK9 levels reduced by 45 to 84 percent and LDL levels reduced by 30 to 60 percent, both clinically relevant and stable reductions. Molecular analyses of biopsied liver tissue also demonstrated that genome editing induced mutations in 40 to 65 percent of the PCSK9 genes. Importantly, the AAV vector doses used in this study have been safely and effectively used in clinical trials of AAV gene replacement therapy for patients with hemophilia.

“Our initial work with several delivery and editing approaches produced the most impressive data in non-human primates when we paired AAV for delivery with the engineered meganuclease for editing,” said senior author James M. Wilson, MD, PhD, a professor of Medicine and Pediatrics and director of the Gene Therapy Program at Penn. “We leveraged our 30-plus years of experience in gene therapy to progress the translational science of in vivo genome editing, and in doing so, reinforced the importance of early studies in nonhuman primates to assess safety and efficacy.”

Future studies will focus on ways to mitigate immune toxicity and the occurrence of editing in targets outside of the desired site within the PCSK9 gene. In addition to patients with hypercholesterolemia, these data should also inform potential use of this approach for a broad spectrum of liver metabolic diseases caused by mutations in other genes.

Source:

https://www.pennmedicine.org/news/news-releases/2018/july/genome-editing-reduces-cholesterol-in-large-animal-model-laying-the-groundwork-for-in-human-trials

Tagged with:

About author

Related Articles