A5090160192- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Cancer, Lipids, and Metabolism
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- ATP Synthase and ATPases Research
- Biosimilars and Bioanalytical Methods
- Diet and metabolism studies
- Metabolomics and Mass Spectrometry Studies
- Amino Acid Enzymes and Metabolism
- Bioactive Compounds and Antitumor Agents
- Liver Disease Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Genetics and Neurodevelopmental Disorders
- Adipose Tissue and Metabolism
- Biochemical Analysis and Sensing Techniques
- Peroxisome Proliferator-Activated Receptors
- Epigenetics and DNA Methylation
- Diet, Metabolism, and Disease
- Endoplasmic Reticulum Stress and Disease
- Folate and B Vitamins Research
- Viral Infectious Diseases and Gene Expression in Insects
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Drug Transport and Resistance Mechanisms
Verve Therapeutics (United States)
2022-2024
Broad Institute
2013-2019
Massachusetts General Hospital
2008-2016
Howard Hughes Medical Institute
2013-2016
Center for Systems Biology
2008-2013
Harvard University
2007-2013
Dana-Farber Cancer Institute
2007-2011
University of Maryland, Baltimore
2011
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
2011
University of California, Los Angeles
2011
Mitochondrial dysfunction is associated with a spectrum of human disorders, ranging from rare, inborn errors metabolism to common, age-associated diseases such as neurodegeneration. How these lesions give rise diverse pathology not well understood, partly because their proximal consequences have been well-studied in mammalian cells. Here we provide two lines evidence that mitochondrial respiratory chain leads alterations one-carbon pathways. First, using hypothesis-generating metabolic,...
VERVE-101 is an investigational in vivo CRISPR base-editing medicine designed to alter a single DNA base the PCSK9 gene, permanently turn off hepatic protein production, and thereby durably lower low-density lipoprotein cholesterol. We test efficacy, durability, tolerability, potential for germline editing of studies nonhuman primates murine F1 progeny study.Cynomolgus monkeys were given intravenous infusion vehicle control (n=10) or at dose 0.75 mg/kg (n=4) 1.5 (n=22) with subsequent...
Despite the role of aerobic glycolysis in cancer, recent studies highlight importance mitochondria and biosynthetic pathways as well. PPARγ coactivator 1α (PGC1α) is a key transcriptional regulator several metabolic including oxidative metabolism lipogenesis. Initial suggested that PGC1α expression reduced tumors compared with adjacent normal tissue. Paradoxically, other show associated cancer cell proliferation. Therefore, especially carcinogenesis unclear. Using Pgc1α(-/-) Pgc1α(+/+) mice,...
Tau hyperphosphorylation is a central event in the development of Alzheimer's Disease (AD). Protein phosphatase 2A (PP2A) heterotrimer formation necessary for efficient dephosphorylation tau protein. S ‐Adenosylmethionine‐dependent carboxyl methylation essential assembly PP2A heterotrimers. Epidemiological evidence indicates that elevated plasma homocysteine an independent risk factor AD. Homocysteine key intermediate methyl cycle and results global decrease cellular methylation. We propose...
Current therapy for lung cancer involves multimodality therapies. However, many patients are either refractory to or develop drug resistance. KRAS and epidermal growth factor receptor (EGFR) mutations represent some of the most common in cancer, studies have shown importance these both carcinogenesis chemoresistance. Genetically engineered murine models mutant EGFR been developed that more accurately recapitulate human cancer. Recently, using cell-based experiments, we showed platinum-based...
Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age onset. Due to their genetic heterogeneity, these are difficult diagnose. We have developed targeted exome sequencing approach improve our ability properly diagnose mitochondrial apply it here an individual patient. Our method targets DNA (mtDNA) the exons 1,600 nuclear genes involved in biology or Mendelian multi-system phenotypes, thereby allowing for...
This study assessed the effectiveness of surgical sympathetic denervation common hepatic artery (CHADN) in improving glucose tolerance. CHADN eliminated norepinephrine content liver and partially decreased it pancreas upper gut. We oral tolerance at baseline after 4 weeks high-fat high-fructose (HFHF) feeding. Dogs were then randomized to sham surgery (SHAM) (n = 9) or 11) retested 2.5 3.5 later while still on HFHF diet. improved by ∼60% part because enhanced insulin secretion, as indicated...
Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion the oxidative phosphorylation system (OXPHOS). Idebenone menadione are redox-active molecules capable rescuing OXPHOS activity by engaging I-independent pathways entry, often referred as "complex bypass." In present study, created a cellular model deficiency using CRISPR genome editing knock out Ndufa9 mouse myoblasts, utilized cell line develop...
Introduction: Maintaining LDL-C at goal levels is critical in populations high risk for cardiovascular events, including people with heterozygous familial hypercholesterolemia (HeFH) and/or premature coronary artery disease (CAD). Despite multiple approved lowering therapies these populations, most patients are not guideline-directed treatment goal. In vivo base editing to inactivate hepatic PCSK9 has the potential provide lifelong after a single course of treatment. Success approach...
This presentation contains "forward-looking statements" within the meaning of Private Securities Litigation Reform Act 1995 that involve substantial risks and uncertainties, including statements regarding safety, tolerability, potential benefits VERVE-101, company's timing ability to enroll patients in its ongoing heart-1 trial, initiation a clinical trial VERVE-102, Company's research development plans, advantages therapeutic programs, VERVE-101 VERVE-102.All statements, other than...
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<p>PDF file - 395K</p>
<div>Abstract<p>Despite the role of aerobic glycolysis in cancer, recent studies highlight importance mitochondria and biosynthetic pathways as well. PPARγ coactivator 1α (PGC1α) is a key transcriptional regulator several metabolic including oxidative metabolism lipogenesis. Initial suggested that PGC1α expression reduced tumors compared with adjacent normal tissue. Paradoxically, other show associated cancer cell proliferation. Therefore, especially carcinogenesis unclear. Using...
<div>Abstract<p>Despite the role of aerobic glycolysis in cancer, recent studies highlight importance mitochondria and biosynthetic pathways as well. PPARγ coactivator 1α (PGC1α) is a key transcriptional regulator several metabolic including oxidative metabolism lipogenesis. Initial suggested that PGC1α expression reduced tumors compared with adjacent normal tissue. Paradoxically, other show associated cancer cell proliferation. Therefore, especially carcinogenesis unclear. Using...
Introduction: VERVE-101 is an in vivo CRISPR base editing therapy designed to alter a single DNA the PCSK9 gene, permanently inactivate hepatic expression, and thereby durably lower LDL cholesterol (LDL-C). Here, we test efficacy, tolerability, potential for germline of studies 43 non-human primates. Methods: Cynomolgus monkeys were dosed with intravenous infusion vehicle control (N = 10) or at dose 0.75 mg/kg 4) 1.5 22) subsequent assessment liver editing, reductions blood LDL-C, safety...