Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies have shown that ultrasound, used either alone or in combination with microbubble contrast agents, can increase cell membrane permeability to plasmid DNA. Because ultrasound is a non-painful and well-established tool in clinical medicine, its potential to enhance DNA uptake into the muscles of patients with muscular dystrophy is conceptually attractive. Therefore, we evaluated the ability of ultrasound pulses (1 MHz; 1.5 W/cm2) to increase exogenous (LacZ) gene expression in normal wild-type and dystrophic Dmd(mdx/mdx) mice after plasmid DNA injection into muscle. We also ascertained whether co-injection of lipid-encapsulated perfluoropropane microbubbles (Definity) or pretreatment with hyaluronidase could further increase the level of gene transfer to ultrasound-treated muscles. The use of ultrasound did not increase transfection efficiency in normal mice. In contrast, dystrophic mice demonstrated an increase in the number of transfected fibers (threefold) as well as the amount of LacZ protein (22-fold) after ultrasound exposure, provided that Definity was also co-injected with the DNA. Pretreatment of muscles with hyaluronidase before ultrasound exposure was not effective in augmenting the level of gene transfer. Under the optimal conditions for dystrophic muscle transfection (ultrasound + Definity), there was no associated increase in muscle damage. Hence ultrasound may provide a safe and effective method for enhancing gene transfer to dystrophic muscles, thereby increasing the prospects for therapeutic application of naked DNA in muscular dystrophy patients.
 ...
PMID:Ultrasound increases plasmid-mediated gene transfer to dystrophic muscles without collateral damage. 1243 62