Navigation Links
'Cookbook recipes' would cure disease with nontoxic DNA delivery systems

Scientists studying the structure and interaction of negatively charged lipids and DNA molecules have created a "cookbook" for a class of nontoxic DNA delivery systems that will assist doctors and clinicians in the safe and effective delivery of genetic medicine.

As reported in the Aug. 9 issue of the Proceedings of the National Academy of Sciences, researchers have now performed a careful, comprehensive study to see how negatively charged lipids stick to negatively charged DNA and self-organize into structures.

"Many research groups have made concoctions with ingredients in different proportions and then assessed their effectiveness in gene delivery, but this is hard and requires a lot of intuition," said Gerard Wong, a professor of materials science and engineering, physics, and bioengineering at the University of Illinois at Urbana-Champaign, and corresponding author of the paper.

"By understanding some of the physics, we now have recipes for assembling delivery systems with different structures, which can have intrinsically different, controllable DNA delivery efficiencies," Wong said. "We found that the same family of structures are generated for many different ions."

Gene therapy is one of the most promising strategies for developing cures for many hereditary and acquired diseases. Protocols have been approved for treating cancer, cystic fibrosis and neuromuscular disorders, for example, but delivering DNA to the proper location and getting the right amount of DNA expression without killing innocent cells has become the Achilles' heel in DNA delivery.

Positively charged (cationic) synthetic molecules will readily bond to negatively charged DNA molecules and have been used for DNA delivery, but these cationic molecules are often toxic to cells, Wong said. An alternative is to use naturally occurring negatively charged (anionic) lipids that won't harm cells.

"The problem then becomes: 'How do you stick a negatively charged lipid to a negatively charged DNA molecule?'" said Wong, who also is a researcher at the Beckman Institute for Advanced Science and Technology. "One idea is to glue the lipids and DNA together with positively charged ions like calcium."

Using synchrotron small angle X-ray scattering and confocal microscopy, Wong and his colleagues -- former Illinois graduate student Hongjun Liang (now a postdoctoral researcher at the University of California at Santa Barbara) and theoretician Daniel Harries at the National Institutes of Health -- investigated how different ion-mediated interactions were expressed in self-assembled anionic lipid-DNA structures.

At low membrane charge densities, for example, anionic lipids and DNA molecules self-assemble into structures with alternating layers of DNA and anionic membranes bound together by cations, Wong said. At high membrane charge densities, there is a surprise: The DNA is expelled, leaving a stack of anionic membranes glued together by cations -- a feature that could prove useful in other controlled drug delivery applications.

The researchers also produced inverted hexagonal structures with encapsulated DNA. "First, the strands of DNA are coated with positively charged ions," Wong said. "The strands are then wrapped with negatively charged lipids and resemble tubes, which are then grouped into hexagonal arrangements."

Utilizing naturally occurring anionic lipids instead of cationic lipids "creates a whole hierarchy of interactions and a much richer range of structures," Wong said, "which really opens up new possibilities."


Source:University of Illinois at Urbana-Champaign

Related biology news :

1. $5.1 billion would save 6 million children
2. President Bushs cut to AIDS prevention in Africa would be devastating
3. Ethical guidelines suggested for research that would put human stem cells in primates
4. Proposal would allow wild animals to roam North America
5. New discovery: If it werent for this enzyme, decomposing pesticide would take millennia
6. Some people would give life or limb not to be fat
7. Designer babies - what would you do for a healthy baby?
8. Smallpox outbreak: How long would it take for vaccines to protect people? Would it work?
9. Neuronal traffic jam marks early Alzheimers disease
10. Scientists detect probable genetic cause of some Parkinsons disease cases
11. Ecological destruction fuels emerging diseases
Post Your Comments:

(Date:10/29/2015)... Today, LifeBEAM , a leader ... a global leader in technical performance sports clothing ... advanced bio-sensing technology. The hat will allow fitness ... biometrics to improve overall training performance. As a ... bring together the most advanced technology, extensive understanding ...
(Date:10/27/2015)... 27, 2015 Munich, Germany ... Mapping technology (ASGM) automatically maps data from mobile eye ... , so that they can be quantitatively analyzed ... Munich, Germany , October 28-29, 2015. SMI,s ... from mobile eye tracking videos created with SMI,s ...
(Date:10/26/2015)... , October 26, 2015 ... --> adds Biometrics Market ... 2021 as well as Emerging Biometrics ... reports to its collection of IT ... . --> ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... Israel , Nov. 24, 2015  Tikcro Technologies Ltd. (OTCQB: TIKRF) ... on December 29, 2015 at 11:00 a.m. Israel ... Electra Tower, 98 Yigal Allon Street, 36 th Floor, ... of Eric Paneth and Izhak Tamir to the ... Rami Skaliter as external directors; , approval of an amendment to ...
(Date:11/24/2015)... , Nov. 24, 2015  Twist Bioscience, ... that Emily Leproust, Ph.D., Twist Bioscience chief executive ... Healthcare Conference on December 1, 2015 at 3:10 ... in New York City. --> ... . Twist Bioscience is on Twitter. Sign ...
(Date:11/24/2015)... ... , ... InSphero AG, the leading supplier of easy-to-use solutions for production, culture, ... serve as Chief Operating Officer. , Having joined InSphero in November 2013 ... was promoted to Head of InSphero Diagnostics in 2014. There she has built ...
(Date:11/24/2015)... Nov. 24, 2015 /CNW Telbec/ - ProMetic Life Sciences Inc. ... that Mr. Pierre Laurin , President and Chief Executive ... the upcoming Piper Jaffray 27 th Annual Healthcare Conference ... December 1-2, 2015. st , at 8.50am ... meetings throughout the day. The presentation will be available live ...
Breaking Biology Technology: