Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antisense oligodeoxynucleotide is a negative charged macromolecule and hence is difficult to penetrate cell membrane and liable to degradation. To increase the effective concentration of antisense drugs in the target cells, a hepatocyte-targeting liposome directed to asialoglycoprotein receptors exclusively expressing on the hepatocyte membrane was designed and prepared based on the receptor-mediated gene transfer. In order to accelerate endosomal exit of nucleic acid drugs, the liposomal formulation with pH-sensitive property was adopted. The hepatocyte-targeting and pH-sensitivity of liposome were analyzed by galactose-receptor competitive inhibition and hemolysis of chicken red blood cell. Antisense oligodeoxynucleotide, HCV363 against HCV 5'NCR, was delivered via prepared liposome to transgenic cell HepG2.9706 and evaluated for its inhibitory effect on luciferase expression controlled by HCV 5'NCR in HepG2.9706 using Luciferase Assay System The results showed that different concentrations (10, 20, 30 mmol/L) of galactose solutions reduce the delivery effects of liposome to some extend that were up to saturation when the concentrations of galactose solution exceed 20 mmol/L. Prepared liposomes mixed with chicken RBC are put into PBS buffers with different pH values(4.0-8.0), it was observed that the amount of heme is greatly released in acidic PBS (pH < 6) due to the fusion of liposome and RBC membranes. Liposome-mediated HCV363 has dose-dependent inhibitory activities on luciferase expression controlled by HCV 5'NCR in HepG2.9706 and the inhibitory rate is 86% at a concentration of 1.0 mumol/L. In conclusion, the liposome is proven to be a hepatocyte-targeting pH-sensitive delivery system that can increase the pharmaceutical effects of antisense drugs.
 ...
PMID:[The inhibitory effects of hepatocyte targeting pH-sensitive liposome mediated phosphorothioate antisense oligonucleotide on gene expression controlled by HCV 5'NCR]. 1191 Jul 53

Wiskott-Aldrich syndrome (WAS) is a life-threatening immunodeficiency caused by mutations within the WAS gene. Viral gene therapy to restore WAS protein (WASp) expression in hematopoietic cells of patients with WAS has the potential to improve outcomes relative to the current standard of care, allogeneic bone marrow transplantation. However, the development of viral vectors that are both safe and effective has been problematic. While use of viral transcriptional promoters may increase the risk of insertional mutagenesis, cellular promoters may not achieve WASp expression levels necessary for optimal therapeutic effect. Here we evaluate a self-inactivating (SIN) lentiviral vector combining a chromatin insulator upstream of a viral MND (MPSV LTR, NCR deleted, dl587 PBS) promoter driving WASp expression. Used as a gene therapeutic in Was-/- mice, this vector resulted in stable WASp+ cells in all hematopoietic lineages and rescue of T and B cell defects with a low number of viral integrations per cell, without evidence of insertional mutagenesis in serial bone marrow transplants. In a gene transfer experiment in non-human primates, the insulated MND promoter (driving GFP expression) demonstrated long-term polyclonal engraftment of GFP+ cells. These observations demonstrate that the insulated MND promoter safely and efficiently reconstitutes clinically effective WASp expression and should be considered for future WAS therapy.
 ...
PMID:Safe and Effective Gene Therapy for Murine Wiskott-Aldrich Syndrome Using an Insulated Lentiviral Vector. 2834 87