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
New biomaterial could replace plastic laminates, greatly reduce pollution
21.09.2017 | Penn State
Stopping problem ice -- by cracking it
21.09.2017 | Norwegian University of Science and Technology
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
21.09.2017 | Physics and Astronomy
21.09.2017 | Life Sciences
21.09.2017 | Health and Medicine