Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Scientists Discover That Shape Matters in DNA Nanoparticle Therapy

Published: Tuesday, October 16, 2012
Last Updated: Tuesday, October 16, 2012
Bookmark and Share
Researchers have discovered how to control the shape of nanoparticles that move DNA through the body and have shown that the shapes of these carriers may make a big difference in how well they work in treating cancer and other diseases.

This study, published in the Oct. 12 online edition of Advanced Materials, is also noteworthy because this gene therapy technique does not use a virus to carry DNA into cells. Some gene therapy efforts that rely on viruses have posed health risks.

“These nanoparticles could become a safer and more effective delivery vehicle for gene therapy, targeting genetic diseases, cancer and other illnesses that can be treated with gene medicine,” said Hai-Quan Mao, an associate professor of materials science and engineering in Johns Hopkins’ Whiting School of Engineering.

Mao, co-corresponding author of the Advanced Materials article, has been developing nonviral nanoparticles for gene therapy for a decade. His approach involves compressing healthy snippets of DNA within protective polymer coatings. The particles are designed to deliver their genetic payload only after they have moved through the bloodstream and entered the target cells. Within the cells, the polymer degrades and releases DNA. Using this DNA as a template, the cells can produce functional proteins that combat disease.

A major advance in this work is that Mao and his colleagues reported that they were able to “tune” these particles in three shapes, resembling rods, worms and spheres, which mimic the shapes and sizes of viral particles. “We could observe these shapes in the lab, but we did not fully understand why they assumed these shapes and how to control the process well,” Mao said. These questions were important because the DNA delivery system he envisions may require specific, uniform shapes.

To solve this problem, Mao sought help about three years ago from colleagues at Northwestern. While Mao works in a traditional wet lab, the Northwestern researchers are experts in conducting similar experiments with powerful computer models.

Erik Luijten, associate professor of materials science and engineering and of applied mathematics at Northwestern’s McCormick School of Engineering and Applied Science and co-corresponding author of the paper, led the computational analysis of the findings to determine why the nanoparticles formed into different shapes.

“Our computer simulations and theoretical model have provided a mechanistic understanding, identifying what is responsible for this shape change,” Luijten said. “We now can predict precisely how to choose the nanoparticle components if one wants to obtain a certain shape.”

The use of computer models allowed Luijten’s team to mimic traditional lab experiments at a far faster pace. These molecular dynamic simulations were performed on Quest, Northwestern’s high-performance computing system. The computations were so complex that some of them required 96 computer processors working simultaneously for one month.

In their paper, the researchers also wanted to show the importance of particle shapes in delivering gene therapy. Team members conducted animal tests, all using the same particle materials and the same DNA. The only difference was in the shape of the particles: rods, worms and spheres.

“The worm-shaped particles resulted in 1,600 times more gene expression in the liver cells than the other shapes,” Mao said. “This means that producing nanoparticles in this particular shape could be the more efficient way to deliver gene therapy to these cells.”

The particle shapes used in this research are formed by packaging the DNA with polymers and exposing them to various dilutions of an organic solvent. DNA’s aversion to the solvent, with the help of the team’s designed polymer, causes the nanoparticles to contract into a certain shape with a “shield” around the genetic material to protect it from being cleared by immune cells.

Lead authors of the Advanced Materials paper were Wei Qu, a graduate student in Luijten’s research group at Northwestern, and Xuan Jian, who was a doctoral student in Mao’s lab. Along with Mao and Luijten, the remaining co-authors of the paper, all from Johns Hopkins, are Deng Pan, who worked on the project as an undergraduate; Yong Ren, a postdoctoral fellow; John-Michael Williford, a biomedical engineering doctoral student; and Honggang Cui, an assistant professor in the Department of Chemical and Biomolecular Engineering.

Initial funding for the research came from a seed grant provided by the Johns Hopkins Institute for NanoBioTechnology, of which Mao is an affiliate. The Johns Hopkins-Northwestern partnership research was supported by a National Institutes of Health grant.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More Than 4,600+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Johns Hopkins Launches Immunotherapy Center
Immunotherapy holds the potential to cure and end all forms of cancer.
Wednesday, March 30, 2016
Biomarker for Recurring HPV-Linked Oropharyngeal Cancers
A look-back analysis of HPV infection antibodies in patients treated for oropharyngeal (mouth and throat) cancers linked to HPV infection suggests at least one of the antibodies could be useful in identifying those at risk for a recurrence of the cancer, say scientists at the Johns Hopkins University.
Tuesday, February 09, 2016
Less May Be More in Slowing Cholera Epidemics
Mathematical model shows more cases may be prevented and more lives saved when using one dose of cholera vaccine instead of recommended two doses.
Thursday, August 27, 2015
'Jumping Genes' Unusually Active In Many GI Cancers
Rogue gene insertions could one day speed diagnosis.
Wednesday, August 19, 2015
p53 Checks Centriole Numbers to Prevent Harmful Cell Divisions
Scientists at Johns Hopkins say they have learned that most cells will not divide without centrioles, and they found out why.
Tuesday, July 07, 2015
New Way of Preventing Diabetes-Associated Blindness
Researchers have discovered a potential treatment for the most common cause of lose of vision in working age adults in the U.S.
Wednesday, May 27, 2015
Collecting Cancer Data in the ‘Cloud’ Could Lead to More Effective Treatment
Storing music and photos on distant computers via “cloud” technology is nothing new. But Johns Hopkins researchers are now using this tactic to collect detailed information from thousands of cancer cell samples.
Tuesday, November 06, 2012
Synthetic Protein Could Lead Doctors to Tumors
Technique using ultraviolet light may lead to new type of diagnostic imaging technology.
Wednesday, September 05, 2012
Scientific News
Platelets are the Pathfinders for Leukocyte Extravasation During Inflammation
Findings from the study could help in the prevention and treatment of inflammatory pathologies.
ASMS 2016: Targeting Mass Spectrometry Tools for the Masses
The expanding application range of MS in life sciences, food, energy, and health sciences research was highlighted at this year's ASMS meeting in San Antonio, Texas.
Benchtop Automation Trends
Gain a better understanding of current interest in and future deployment of benchtop automated systems.
How Cancer Spreads in the Body
Cancer cells appear to depend on an unusual survival mechanism to spread around the body, according to an early study led by Queen Mary University of London.
Fix for 3-Billion-Year-Old Genetic Error
Researchers at The University of Texas at Austin have developed a fix that allows RNA to accurately proofread for the first time.
“Amazing Protein Diversity” Discovered in Maize
The genome of the corn plant – or maize, as it’s called almost everywhere except the US – “is a lot more exciting” than scientists have previously believed. So says the lead scientist in a new effort to analyze and annotate the depth of the plant’s genetic resources.
Manufactured Stem Cells to Advance Clinical Research
Clinical-grade cell line will enable development of new therapies and accelerate early-stage clinical research.
Dengue Virus Exposure May Amplify Zika Infection
Researchers at Imperial College London have found that the previous exposure to the dengue virus may increase the potency of Zika infection.
Gender Determination in Forensic Investigations
This study investigated the effectiveness of lip print analysis as a tool in gender determination.
Identifying Novel Types of Forensic Markers in Degraded DNA
Scientists have tried to verify the nucleosome protection hypothesis by discovering STRs within nucleosome core regions, using whole genome sequencing.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,600+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!