A5088266291- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- NF-κB Signaling Pathways
- Animal Genetics and Reproduction
- RNA modifications and cancer
- Immune Response and Inflammation
- interferon and immune responses
- RNA and protein synthesis mechanisms
- Biomedical Ethics and Regulation
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- Cytokine Signaling Pathways and Interactions
- Biotechnology and Related Fields
- Animal Virus Infections Studies
- HIV Research and Treatment
- Cancer-related Molecular Pathways
- Viral Infectious Diseases and Gene Expression in Insects
- T-cell and Retrovirus Studies
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Bacteriophages and microbial interactions
- Genomics and Chromatin Dynamics
- Biomedical and Engineering Education
Salk Institute for Biological Studies
2013-2023
Sir Ganga Ram Hospital
2023
Narayana Nethralaya
2020
Aalto University
2019
University of California, San Diego
1986-2018
Arcturus Therapeutics (United States)
2017
Torrey Pines Institute For Molecular Studies
1999-2016
American Cancer Society
1996-2016
University of Southern California
1976-2015
Kyushu University
2014
A retroviral vector system based on the human immunodeficiency virus (HIV) was developed that, in contrast to a murine leukemia virus-based counterpart, transduced heterologous sequences into HeLa cells and rat fibroblasts blocked cell cycle, as well primary macrophages. Additionally, HIV could mediate stable vivo gene transfer terminally differentiated neurons. The ability of HIV-based viral vectors deliver genes nondividing increase applicability therapy.
Tumor necrosis factor α (TNF-α) signaling gives rise to a number of events, including activation transcription NF-κB and programmed cell death (apoptosis). Previous studies TNF-α have suggested that these two events occur independently. The sensitivity kinetics TNF-α-induced apoptosis are shown be enhanced in types expressing dominant-negative IκBα (IκBαM). These findings suggest negative feedback mechanism results from which suppresses the signals for death.
We describe the construction of a safe, replication-defective and efficient lentiviral vector suitable for in vivo gene delivery. The reverse transcription was found to be rate-limiting step; therefore, promoting reaction inside particles before delivery significantly enhanced efficiency transfer. After injection into brain adult rats, sustained long-term expression transgene obtained absence detectable pathology. A high proportion neurons areas surrounding sites expressed transduced...
ABSTRACT We have constructed a new series of lentivirus vectors based on human immunodeficiency virus type 1 (HIV-1) that can transduce nondividing cells. The U3 region the 5′ long terminal repeat (LTR) in vector constructs was replaced with cytomegalovirus (CMV) promoter, resulting Tat-independent transcription but still maintaining high levels expression. A self-inactivating (SIN) by deleting 133 bp 3′ LTR, including TATA box and binding sites for factors Sp1 NF-κB. deletion is transferred...
Phosphorylation of inhibitor kappa B (IkappaB) proteins is an important step in the activation transcription nuclear factor (NF-kappaB) and requires two IkappaB kinases, IKK1 (IKKalpha) IKK2 (IKKbeta). Mice that are devoid gene had extensive liver damage from apoptosis died as embryos, but these mice could be rescued by inactivation encoding tumor necrosis receptor 1. Mouse embryonic fibroblast cells were isolated IKK2-/- embryos showed a marked reduction factor-alpha (TNF-alpha)-...
Cellular oncogenes have been implicated in the induction of malignant transformation some model systems vitro and may be related to malignancies vivo vertebrate species. This article describes a study expression 15 cellular fresh human tumors from 54 patients, representing 20 different tumor types. More than one oncogene was transcriptionally active all examined. In 14 patients it possible normal tissue same organ. many these transcriptional activity certain greater tissue. The fes (feline...
We have developed an efficient and reproducible method for RNA transfection, using a synthetic cationic lipid, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA), incorporated into liposome (lipofectin). Transfection of 10 ng to 5 micrograms Photinus pyralis luciferase mRNA synthesized in vitro NIH 3T3 mouse cells yields linear response activity. The procedure can be used efficiently transfect human, rat, mouse, Xenopus, Drosophila cells. Using the RNA/lipofectin...
We describe the construction and characterization of retroviral vectors packaging plasmids that produce helper-free retrovirus with titers 1 X 10(6) to 5 within 48 h. These contain immediate early region human cytomegalovirus enhancer-promoter fused Moloney murine leukemia virus long terminal repeat at TATA box in 5' U3 region, yielding pCL promoter. By selecting designed express genes from one four promoters (dihydrofolate reductase, Rous sarcoma virus, repeat, or cytomegalovirus), system...
The identification of monogenic and complex genes responsible for neurological disorders requires new approaches delivering therapeutic protein to significant numbers cells in the central nervous system. A lentivirus-based vector capable infecting dividing quiescent was investigated vivo by injecting highly concentrated viral stock into striatum hippocampus adult rats. Control brains were injected with a Moloney murine leukemia virus, adenovirus, or adeno-associated virus vector. volumes...
A 12.0-kilobase EcoRI restriction fragment containing FBJ murine osteosarcoma virus (FBJ-MSV) proviral DNA was identified in FBJ-MSV-transformed nonproducer rat cells and molecularly cloned bacteriophage Charon 30 (lambda FBJ-1). 5.8-kb HindIII the entire FBJ-MSV isolated from lambda FBJ-1 subsequently subcloned plasmid pBR322 (pFBJ-2). The recombinant pFBJ-2 able to induce morphological transformation of fibroblasts tissue culture. Transfected contained p55 p39 antigens specific for...
Efficient gene transfer into human hematopoietic stem cells (HSCs) is an important goal in the study of system as well for therapy disorders. A lentiviral vector based on immunodeficiency virus (HIV) was able to transduce CD34+ capable stable, long-term reconstitution nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. High-efficiency transduction occurred absence cytokine stimulation and resulted transgene expression multiple lineages up 22 weeks after transplantation.