A5038704186- Virus-based gene therapy research
- Hemophilia Treatment and Research
- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- CAR-T cell therapy research
- Ultrasound Imaging and Elastography
- CRISPR and Genetic Engineering
- Cancer-related gene regulation
- Coronary Interventions and Diagnostics
- Blood properties and coagulation
- RNA Interference and Gene Delivery
- Photoacoustic and Ultrasonic Imaging
- Venous Thromboembolism Diagnosis and Management
- Ultrasound and Hyperthermia Applications
- Blood groups and transfusion
- Viral gastroenteritis research and epidemiology
- Animal Genetics and Reproduction
- Cell Adhesion Molecules Research
- Cardiovascular Health and Disease Prevention
- Acute Myocardial Infarction Research
- Cerebrovascular and Carotid Artery Diseases
- Atherosclerosis and Cardiovascular Diseases
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Lung Cancer Research Studies
University of North Carolina at Chapel Hill
2015-2024
Pfizer (United States)
2002-2021
University of North Carolina Health Care
2011-2019
Pfizer (South Korea)
2018
Samsung Medical Center
2018
Analysis Group (United States)
2015
Rosalind Franklin University of Medicine and Science
1994-2015
UNC/NCSU Joint Department of Biomedical Engineering
2014
Reinertsen (Norway)
2011
University of Copenhagen
2011
The aim of this study was to determine whether recurrent intravenous injections with Porphyromonas gingivalis (P gingivalis), mimicking periodontitis-associated bacteremia, promotes coronary artery and aortic atherosclerosis in pigs.Pigs (n=36) fed low- or high-fat chow were divided into P gingivalis-sensitized gingivalis-challenged groups controls saline-treated controls. Pigs sensitized 10(9) killed subcutaneously. Four weeks later all pigs the group be challenged started thrice weekly for...
Abstract Lentiviral vectors are attractive tools for liver-directed gene therapy because of their capacity stable expression and the lack preexisting immunity in most human subjects. However, use integrating may raise some concerns about potential risk insertional mutagenesis. Here we investigated liver transfer by integrase-defective lentiviral (IDLVs) containing an inactivating mutation integrase (D64V). Hepatocyte-targeted using IDLVs resulted sustained robust induction immune tolerance...
Gene therapy with lentiviral vectors targeting transgene expression to hepatocytes provides stable reconstitution of clotting activity in dogs hemophilia B and does not show genotoxicity tumor-prone mice.
It is essential to improve therapies for controlling excessive bleeding in patients with haemorrhagic disorders. As activated blood platelets mediate the primary response vascular injury, we hypothesize that storage of coagulation Factor VIII within may provide a locally inducible treatment maintain haemostasis haemophilia A. Here show haematopoietic stem cell gene therapy can prevent occurrence severe episodes dogs A at least 2.5 years after transplantation. We employ clinically relevant...
We demonstrate that a single intraportal vein injection of recombinant adeno-associated virus (rAAV) vector encoding canine factor IX (cFIX) cDNA under the control liver-specific enhancer/promoter leads to long-term correction bleeding disorder in hemophilia B dogs. Stable expression therapeutic level cFIX (5% normal level) was detected plasma dog injected with an AAV at dose 4.6 × 1012 particles/kg for over 7 months. Both whole-blood clotting time (WBCT) and activated partial thromboplastin...
Both acute coronary occlusion and reperfusion of an infarct-related artery lead to significant myocardial cell death. Recent evidence has been presented that activation the transcription factor nuclear factor-κB (NF-κB) plays a critical role in injury. NF-κB is usually bound its inhibitor, IκB, classic occurs when 20S proteasome degrades IκB phosphorylated ubiquitinated. In this study, was inhibited by systemic administration inhibitor (PS-519) porcine model The experimental protocol induced...
A potential consequence of systemic administration viral vectors is the inadvertent introduction foreign DNA into recipient germ cells. To evaluate safety in vivo recombinant adeno-associated virus (rAAV) mediated gene transfer approaches for hemophilia B, we explored risk germline transmission vector sequences following intramuscular (IM) injection rAAV four species male animals (mouse, rat, rabbit and dog). In biodistribution studies mice rats, there a dose-dependent increase likelihood...
Intramuscular injection of an adeno-associated virus (AAV) vector has resulted in dose-dependent, stable expression canine factor IX (cF.IX) hemophilia B dogs with F.IX missense mutation (Herzog et al ., Nat. Med. 1999;5:56-63). The use a species-specific transgene allowed us to study risks and characteristics antibody formation against the therapeutic product. We analyzed seven that had been injected at single time point multiple intramuscular sites varying doses (dose per kilogram, dose...
Developing adeno-associated viral (AAV)-mediated gene therapy for hemophilia A (HA) has been challenging due to the large size of factor VIII (FVIII) complementary DNA and concern development inhibitory antibodies FVIII in HA patients. Here, we perform a systematic study dogs by delivering canine (cFVIII) transgene either as single chain or two chains an AAV vector. An optimized cFVIII delivered using serotype 8 (AAV8) peripheral vein injection resulted dose-response with sustained...
Recent progress in engineering the genomes of large animals has spurred increased interest developing better animal models for diseases where current options are inadequate. Here, we report creation Yucatan miniature pigs with targeted disruptions low-density lipoprotein receptor (LDLR) gene an effort to provide improved model familial hypercholesterolemia and atherosclerosis. well established as translational research because similarities humans physiology, anatomy, genetics, size. Using...