Navigation Links
Bare metal stents deliver gene therapy to heart vessels with less inflammation in animal studies

Improved materials may allow stents, tiny metal scaffolds inserted into blood vessels, to better deliver beneficial genes to patients with heart disease, by reducing the risk of inflammation that often negates initial benefits. The new technique, using a compound that binds in an extremely thin layer to bare metal surfaces, may have potential uses in other areas of medicine that make use of metallic implants.

Cardiologists frequently treat heart disease patients now by using stents to expand partially blocked blood vessels and improve blood flow. However, new obstructions may gradually form within the stents themselves and dangerously narrow the passageway. A newer generation of stents releases drugs to counteract this renarrowing process, called restenosis, but the polymer coatings that initially hold the drugs to the stents may stimulate inflammation. The inflammation in turn leads to restenosis.

Researchers at The Children's Hospital of Philadelphia have developed a novel technique to attach therapeutic genes to a stent's bare metal surface. This technique allows the genes to help heal the surrounding blood vessels, while avoiding the inflammation caused by polymer coatings.

The research team reported their proof-of-principle study, using cell culture and animal models, in the early edition of the Proceedings of the National Academy of Sciences, published online this week.

"This is the first study to demonstrate successful delivery of a gene vector from a bare metal surface," said senior author Robert J. Levy, M.D., the William J. Rashkind Chair of Pediatric Cardiology at The Children's Hospital of Philadelphia. A gene vector is a biological substance, in this case an adenovirus, capable of delivering a therapeutic gene to target cells.

Dr. Levy's team created a unique water-soluble compound, polyallylamine biphosphonate, that binds to the stent's metal alloy surface in a layer with the thickness of only a single molecule. The biphosphonate holds and gradually releases adenovirus particles of the type used to deliver therapeutic genes.

In cell cultures, the adenovirus successfully delivered genes from alloy samples to animal arterial smooth muscle cells. In a second experiment using rodents, the researchers detected gene expression with significantly lower restenosis in the carotid arteries of animals with the experimental stents, compared to control animals with conventional, polymer-coated stents.

The researchers used a therapeutic gene that encodes for a protein, inducible nitric oxide synthase (iNOS), in the carotid artery studies, because of iNOS's ability to control cell damage in blood vessels. "However, in further studies, one might use a combination of therapeutic genes or different gene vectors, for even better results," said Dr. Levy.

Metallic implants are already widely used in medicine. Some examples are artificial joints and orthopedic pins and rods, pacemaker electrodes, and titanium tooth implants. "The results of our study may have broader implications for other diseases in which implantable medical devices may be used to deliver gene therapy," said Dr. Levy.

Dr. Levy's co-authors included Ilia Fishbein, M.D., Ivan S. Alferiev, M.D., Origene Nyanguile, Richard Gaster, and Howard Felderman, of the Children's Hospital Division of Cardiology. Co-authors from the University of Pennsylvania were John M. Vohs and Gordon S. Wong, of the Department of Chemical and Biomolecular Engineering; Hoon Choi and I-Wei Chen, of the Department of Material Science and Engineering; and Robert L. Wilensky, of the Cardiovascular Division of the Hospital of the University of Pennsylvania.


Source:Children's Hospital of Philadelphia

Related biology news :

1. Defenseless plants arm themselves with metals
2. Encoded metallic nanowires reveal bioweapons
3. Particle size matters to bacteria ability to immobilize heavy metals
4. New methods of gene delivery using lasers
5. Recombinant DNA technology may enable oral, rather than injectable, delivery of protein drugs
6. Self-assembled DNA buckyballs for drug delivery
7. New research could help us deliver genes for new bone formation
8. Cookbook recipes would cure disease with nontoxic DNA delivery systems
9. Discarded placentas deliver researchers promising cells similar to embryonic stem cells
10. Targeted drug delivery achieved with nanoparticle-aptamer bioconjugates
11. Cellular scale drug delivery from the inside out
Post Your Comments:

(Date:10/27/2015)... NEW YORK , Oct. 27, 2015 ... the major issues of concern for various industry verticals ... This is due to the growing demand for secure ... practices in various ,sectors, such as hacking of bank ... concerns for electronic equipment such as PC,s, laptops, and ...
(Date:10/27/2015)... Oct. 27, 2015 Synaptics Inc. (NASDAQ: SYNA ... that Google has adopted the Synaptics ® ClearPad ... to power its newest flagship smartphones, the Nexus 5X ... --> --> Synaptics ... provide strategic collaboration in the joint development of next ...
(Date:10/26/2015)... Calif. and LAS VEGAS ... Nok Nok Labs , an innovator in modern authentication ... , today announced the launch of its latest version ... unified platform enabling organizations to use standards-based authentication that ... Nok Nok S3 Authentication Suite is ideal for organizations ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... ... November 24, 2015 , ... The United States Golf ... the 2016 USGA Green Section Award. Presented annually since 1961, the USGA Green Section ... her work with turfgrass. , Clarke, of Iselin, N.J., is an extension ...
(Date:11/24/2015)... VANCOUVER , Nov. 24, 2015 /CNW/ - iCo ... ICOTF), today reported financial results for the quarter ... are expressed in Canadian dollars and presented under ... the United States ," said Andrew ... "These advancements regarding iCo-008 are not only value ...
(Date:11/24/2015)... Nov. 24, 2015 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: ... on behalf of the Toronto Stock Exchange, confirms that ... are no corporate developments that would cause the recent ... --> --> About Aeterna Zentaris Inc. ... --> Aeterna Zentaris is a specialty biopharmaceutical ...
(Date:11/24/2015)... ... November 24, 2015 , ... This fall, global software solutions leader SAP ... states to develop and pitch their BIG ideas to improve health and wellness in ... for votes to win the title of SAP's Teen Innovator, an all-expenses paid trip ...
Breaking Biology Technology: