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.
Credits: Wei Qu, Northwestern University, simulation cartoons; Xuan Jiang, Johns Hopkins University, microscopic images.
This illustration depicts DNA molecules (light green), packaged into nanoparticles by using a polymer with two different segments. One segment (teal) carries a positive charge that binds it to the DNA, and the other (brown) forms a protective coating on the particle surface. By adjusting the solvent surrounding these molecules, the Johns Hopkins and Northwestern researchers were able to control the shape of the nanoparticles. The team’s animal tests showed that a nanoparticle’s shape could dramatically affect how effectively it delivers gene therapy to the cells. The cartoon images in the foreground, obtained though computational modeling, matched closely with the gray background images, which were collected through transmission electron microscopy.
“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.
Color available of nanoparticles image; contact Phil Sneiderman or Megan Fellman.Related links:
Johns Hopkins Department of Materials Science and Engineering: http://materials.jhu.edu/
Northwestern University Department of Materials Science and Engineering: http://matsci.northwestern.edu/
Johns Hopkins Institute for NanoBioTechnology: http://inbt.jhu.edu/
Johns Hopkins University news releases can be found on the World Wide Web at http://www.jhu.edu/news_info/news/ Information on automatic E-mail delivery of science and medical news releases is available at the same address.
Phil Sneiderman | Newswise Science News
Researchers invent process to make sustainable rubber, plastics
25.04.2017 | University of Delaware
Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging
24.04.2017 | Pohang University of Science & Technology (POSTECH)
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
25.04.2017 | Physics and Astronomy
25.04.2017 | Materials Sciences
25.04.2017 | Life Sciences