Using a new gene-editing system based on bacterial proteins, MIT researchers have cured mice of a rare liver disorder caused by a single genetic mutation.
The findings, described in the March 30 issue of Nature Biotechnology, offer the first evidence that this gene-editing technique, known as CRISPR, can reverse disease symptoms in living animals. CRISPR, which offers an easy way to snip out mutated DNA and replace it with the correct sequence, holds potential for treating many genetic disorders, according to the research team.
“What’s exciting about this approach is that we can actually correct a defective gene in a living adult animal,” says Daniel Anderson, the Samuel A. Goldblith Associate Professor of Chemical Engineering at MIT, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the paper.
Nanoparticles that deliver short strands of RNA offer a way to treat cancer and other diseases by shutting off malfunctioning genes. Although this approach has shown some promise, scientists are still not sure exactly what happens to the nanoparticles once they get inside their target cells.
A new study from MIT sheds light on the nanoparticles’ fate and suggests new ways to maximize delivery of the RNA strands they are carrying, known as short interfering RNA (siRNA).
“We’ve been able to develop nanoparticles that can deliver payloads into cells, but we didn’t really understand how they do it,” says Daniel Anderson, the Samuel Goldblith Associate Professor of Chemical Engineering at MIT. “Once you know how it works, there’s potential that you can tinker with the system and make it work better.”
Anderson, a member of MIT’s Koch Institute for Integrative Cancer Research and MIT’s Institute for Medical Engineering and Science, is the leader of a research team that set out to examine how the nanoparticles and their drug payloads are processed at a cellular and subcellular level. Their findings appear in the June 23 issue of Nature Biotechnology. Robert Langer, the David H. Koch Institute Professor at MIT, is also an author of the paper....
For Type 1 diabetes sufferers, constant monitoring of insulin and blood sugar levels is both inconvenient and time consuming. But now there is some good news: An MIT project currently underway could allow the body to do it automatically.
MIT researchers have created a type of nanoparticle—for those of us not enrolled at MIT, that’s an extremely tiny particle often used in biomedical research—that can determine when glucose levels in the blood are off and immediately trigger the secretion of enough insulin (which breaks down glucose and gets blood sugar levels under control) to stop the problem. In essence, the particles, which are used to create a toothpaste-consistency gel, are mimicking the role of the pancreas, which is the organ that malfunctions in those who suffer from diabetes. A report from MIT quotes chemical engineering professor Daniel Anderson, who is involved in the research:
“Insulin really works, but the problem is people don’t always get the right amount of it. With this system of extended release, the amount of drug secreted is proportional to the needs of the body,” says Daniel Anderson, an associate professor of chemical engineering and member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science....
Injectable nanoparticles developed at MIT may someday eliminate the need for patients with Type 1 diabetes to constantly monitor their blood-sugar levels and inject themselves with insulin.
The nanoparticles were designed to sense glucose levels in the body and respond by secreting the appropriate amount of insulin, thereby replacing the function of pancreatic islet cells, which are destroyed in patients with Type 1 diabetes. Ultimately, this type of system could ensure that blood-sugar levels remain balanced and improve patients’ quality of life, according to the researchers.
“Insulin really works, but the problem is people don’t always get the right amount of it. With this system of extended release, the amount of drug secreted is proportional to the needs of the body,” says Daniel Anderson, an associate professor of chemical engineering and member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.
Anderson is the senior author of a paper describing the new system in a recent issue of the journal ACS Nano. Lead author of the paper is Zhen Gu, a former postdoc in Anderson’s lab. The research team also includes Robert Langer, the David H. Koch Institute Professor at MIT, and researchers from the Department of Anesthesiology at Boston Children’s Hospital....
Modern medicine is largely based on treating patients with “small-molecule” drugs, which include pain relievers like aspirin and antibiotics such as penicillin.
Those drugs have prolonged the human lifespan and made many life-threatening ailments easily treatable, but scientists believe the new approach of nanoscale drug delivery can offer even more progress. Delivering RNA or DNA to specific cells offers the promise of selectively turning genes on or off, while nanoscale devices that can be injected or implanted in the body could allow doctors to target drugs to specific tissues over a defined period of time.
“There’s a growing understanding of the biological basis of disease, and a growing understanding of the roles certain genes play in disease,” says Daniel Anderson, the Samuel A. Goldblith Associate Professor of Chemical Engineering and a member of MIT’s Institute for Medical Engineering and Science and David H. Koch Institute for Integrative Cancer Research. “The question is, ‘How can we take advantage of this?’”
Researchers in Anderson’s lab, as well as many others at MIT, are working on new ways to deliver RNA and DNA to treat a variety of diseases. Cancer is a primary target, but deliveries of genetic material could also help with many diseases caused by defective genes, including Huntington’s disease and hemophilia. “There are many genes that we think if we could just turn them off or turn them on, it could be therapeutic,” Anderson says....
MIT engineers have created a new polymer film that can generate electricity by drawing on a ubiquitous source: water vapor.
The new material changes its shape after absorbing tiny amounts of evaporated water, allowing it to repeatedly curl up and down. Harnessing this continuous motion could drive robotic limbs or generate enough electricity to power micro- and nanoelectronic devices, such as environmental sensors.
“With a sensor powered by a battery, you have to replace it periodically. If you have this device, you can harvest energy from the environment so you don’t have to replace it very often,” says Mingming Ma, a postdoc at MIT’s David H. Koch Institute for Integrative Cancer Research and lead author of a paper describing the new material in the Jan. 11 issue of Science.
“We are very excited about this new material, and we expect as we achieve higher efficiency in converting mechanical energy into electricity, this material will find even broader applications,” says Robert Langer, the David H. Koch Institute Professor at MIT and senior author of the paper. Those potential applications include large-scale, water-vapor-powered generators, or smaller generators to power wearable electronics.
Other authors of the Science paper are Koch Institute postdoc Liang Guo and Daniel Anderson, the Samuel A. Goldblith Associate Professor of Chemical Engineering and a member of the Koch Institute and MIT’s Institute for Medical Engineering and Science....
Using a technique known as “nucleic acid origami,” chemical engineers have built tiny particles made out of DNA and RNA that can deliver snippets of RNA directly to tumors, turning off genes expressed in cancer cells.
To achieve this type of gene shutdown, known as RNA interference, many researchers have tried — with some success — to deliver RNA with particles made from polymers or lipids. However, those materials can pose safety risks and are difficult to target, says Daniel Anderson, an associate professor of health sciences and technology and chemical engineering, and a member of the David H. Koch Institute for Integrative Cancer Research at MIT.
The new particles, developed by researchers at MIT, Alnylam Pharmaceuticals and Harvard Medical School, appear to overcome those challenges, Anderson says. Because the particles are made of DNA and RNA, they are biodegradable and pose no threat to the body. They can also be tagged with molecules of folate (vitamin B9) to target the abundance of folate receptors found on some tumors, including those associated with ovarian cancer — one of the deadliest, hardest-to-treat cancers....
Drugs made of protein have shown promise in treating cancer, but they are difficult to deliver because the body usually breaks down proteins before they reach their destination.
To get around that obstacle, a team of MIT researchers has developed a new type of nanoparticle that can synthesize proteins on demand. Once these “protein-factory” particles reach their targets, the researchers can turn on protein synthesis by shining ultraviolet light on them.
The particles could be used to deliver small proteins that kill cancer cells, and eventually larger proteins such as antibodies that trigger the immune system to destroy tumors, says Avi Schroeder, a postdoc in MIT’s David H. Koch Institute for Integrative Cancer Research and lead author of a paper appearing in the journal NanoLetters.
“This is the first proof of concept that you can actually synthesize new compounds from inert starting materials inside the body,” says Schroeder, who works in the labs of Robert Langer, MIT’s David H. Koch Institute Professor, and Daniel Anderson, an associate professor of health sciences and technology and chemical engineering.
Langer and Anderson are also authors of the paper, along with former Koch Institute postdocs Michael Goldberg, Christian Kastrup and Christopher Levins...
Photonic crystals are exotic materials with the ability to guide light beams through confined spaces and could be vital components of low-power computer chips that use light instead of electricity. Cost-effective ways of producing them have proved elusive, but researchers have recently been turning toward a surprising source for help: DNA molecules.
In a paper that appeared Oct. 18 in the journal Nature Materials, MIT researchers, together with colleagues at the Scripps Research Institute and the University of Rochester, demonstrated that tiny particles of gold and balls of protein known as virus-like particles, both with strands of DNA attached to them, would spontaneously organize themselves into a lattice-like structure. Although the materials themselves aren’t useful for making photonic crystals, the distances between the particles are exactly those that would enable a photonic crystal to guide light in the visible spectrum....
Using short snippets of RNA to turn off a specific gene in certain immune cells, scientists have shown that they can shut off the inflammation responsible for diseases such as atherosclerosis.
This technique, known as RNA interference, offers a targeted way to stop inflammation and could be useful in treating not only atherosclerosis, but also other forms of heart disease as well as cancer, according to the researchers.
Since RNA interference was discovered in 1998, its ability to potentially shut off any gene in the body has intrigued scientists. RNA interference works by disrupting the flow of genetic information from a cell’s nucleus to its protein-building machinery. The key to success is finding a safe and effective way to deliver short strands of RNA that can bind with and destroy messenger RNA, which carries instructions from the nucleus.
In a study appearing in the Oct. 9 issue of Nature Biotechnology, the researchers delivered short strands of RNA packaged in a layer of fat-like molecules called lipidoids. These RNA-delivering nanoparticles successfully reduced inflammation in mice, without side effects.
The research team includes MIT’s Daniel Anderson, associate professor in the Harvard-MIT Division of Health Sciences and Technology, and Institute Professor Robert Langer, as well as scientists from Massachusetts General Hospital, Harvard Medical School, Brigham and Women’s Hospital, Alnylam Pharmaceuticals, Harrison School of Pharmacy and Seoul National University in South Korea....
A single cancer cell may harbor dozens or even hundreds of mutant genes. Some of those genes instruct the cell to grow abnormally large, others tell it to divide repeatedly or to detach itself and roam the body looking for a new home.
What if you could shut off one, two or even a dozen of those genes, all at once? Some scientists believe that they will soon be able to do just that through RNA interference, a natural process that happens within cells. MIT Institute Professor Phillip Sharp calls it one of the most promising new cancer treatments in development.
For a cell to fulfill its genetic fate, information must be carried from DNA in the nucleus to the ribosome, the part of a cell where proteins are made. RNA interference disrupts this flow via snippets of genetic material, known as siRNA (short interfering RNA). SiRNA binds to messenger RNA (mRNA) molecules, destroying the mRNA before it can deliver instructions to the ribosome.
“It offers the potential to turn off essentially any gene in a cell,” says Daniel Anderson, a member of MIT’s David H. Koch Institute for Integrative Cancer Research. That means scientists can try to shut off the genes that cause cancer cells to go haywire, growing out of control and breaking free from their usual constraints to travel through the body to start new tumors....
Human pluripotent stem cells, which can become any other kind of body cell, hold great potential to treat a wide range of ailments, including Parkinson’s disease, multiple sclerosis and spinal cord injuries. However, scientists who work with such cells have had trouble growing large enough quantities to perform experiments — in particular, to be used in human studies.
Furthermore, most materials now used to grow human stem cells include cells or proteins that come from mice embryos, which help stimulate stem-cell growth but would likely cause an immune reaction if injected into a human patient.
To overcome those issues, MIT chemical engineers, materials scientists and biologists have devised a synthetic surface that includes no foreign animal material and allows stem cells to stay alive and continue reproducing themselves for at least three months. It’s also the first synthetic material that allows single cells to form colonies of identical cells, which is necessary to identify cells with desired traits and has been difficult to achieve with existing materials.
The research team, led by Professors Robert Langer, Rudolf Jaenisch and Daniel G. Anderson, describes the new material in the Aug. 22 issue of Nature Materials. First authors of the paper are postdoctoral associates Ying Mei and Krishanu Saha....
Ever since RNA interference was discovered, in 1998, scientists have been pursuing the tantalizing ability to shut off any gene in the body — in particular, malfunctioning genes that cause diseases such as cancer.
This week, researchers at MIT and Alnylam Pharmaceuticals report that they have successfully used RNA interference to turn off multiple genes in the livers of mice, an advance that could lead to new treatments for diseases of the liver and other organs.
The new delivery method, described in the Proceedings of the National Academy of Sciences, is orders of magnitude more effective than previous methods, says Daniel Anderson, senior author of the paper and a biomedical engineer at the David H. Koch Institute for Integrative Cancer Research at MIT. It’s also the first method that can deliver as many as five genes — previous delivery vehicles could carry only one or two genes....