Nanobiotechnology December 2013/January 2014 Viewpoints
2013: The Year in Review
The rapid development of nanotechnology continued in 2013, and the number of applications and industries incorporating the technology increased. In April 2013, BCC Research predicted that the market for nanomagnetic materials and devices would increase to more than $9 billion by 2017 from an estimated $7.2 billion in 2012. Much of this industry consists of devices for data storage, but the fastest-growing market is for sensing and diagnostic applications, which BCC expects to grow to $108 million by 2017.
However, some pioneering companies attempting to commercialize nanotechnology applications have struggled in 2013. One of the first nanotechnology companies in the United States—NanoInk, which specialized in nanotechnology for industries including life sciences and pharmaceuticals—filed for bankruptcy in April 2013. Dexter Johnson of UK consultancy Cientifica believes that NanoInk's nanolithography dip pen was not scalable and that the company was trying to cover too many markets rather than focusing on a targeted market—a trap into which Johnson thinks many nanotechnology companies fall. Oxford Nanopore Technologies hopes that it will not meet the same fate. The company has been cautious in its approach to developing DNA-sequencing devices that use nanopores; the company originally intended to release its MinION and GridION platforms in 2012 but abandoned this idea in order to reduce the error rates on the devices. At long last, Oxford Nanopore announced in November 2013 that it is opening registration for its MinION Access Programme that will enable life-sciences researchers to try out the device in 2014.
Nanotechnology is pushing forward a number of approaches for managing medical conditions. One such example is in treating Type 1 diabetes. Researchers at the Massachusetts Institute of Technology created injectable nanoparticles in 2013 that imitate the pancreas. The nanoparticles consist of modified dextran and glucose-oxidase enzymes encompassing insulin. The scientists coat each nanoparticle in positively charged chitosan or negatively charged alginate, which causes the nanoparticles to form a polymeric network. When high levels of glucose are present in the blood, the glucose oxidase causes the conversion of the glucose to gluconic acid, leading to an acidic environment that degrades the nanoparticles and releases the insulin. This system has the potential to enable diabetes sufferers to receive the correct dose of insulin proportional to their glucose levels. The researchers think the nanoparticles could work in a patient for a week. However, this technology needs to overcome a large number of hurdles before it finds commercial use—particularly because it is an in vivo system.
Nanotechnology is also finding use as a system for aiding the penetration of substances across the skin and into the body, with a number of developments in 2013. The University of Kentucky developed an electro-osmotic patch consisting of a membrane of billions of carbon nanotubes. The application of a voltage across the nanotubes enables the pumping of uncharged molecules along the nanotubes and into the skin. A watch battery can power the patch for up to ten days, and the researchers have been testing a Bluetooth-enabled version on animals in order to develop a remote-controlled device. The patch could aid in the timed delivery of pain medication or serve as a sophisticated nicotine patch that releases a limited dose at flexible times, helping users to break their addictions.
Other research institutions are working with companies to investigate nanosize molecules to assist in skin penetration. Scientists at the University of California, Santa Barbara, are working with Convoy Therapeutics—which Professor Samir Mitragotri of the University of California founded in 2011—to create skin-penetration delivery systems. In a paper in the January 2014 issue of the Journal of Controlled Release, the team described the use of SPACE (skin-penetrating and cell-entering) peptides to deliver hyaluronic acid across porcine skin. The scientists found that the peptide increased the penetration of hyaluronic acid into the epidermis and dermis fivefold. Although the SPACE peptide does not enable delivery to the bloodstream, it could find use for treating skin ailments and in cosmetics. The University of California's spinout will help to push the technology toward commercialization. In October 2013, the company announced that it had signed a deal with South Korean cosmeceutical company Hugel for the joint development and marketing of Convoy's wrinkle-reduction product.
Pharmaceuticals and Diagnostics
RNA research received significant interest in 2013. Moderna Therapeutics won funding of up to $25 million from the US government in October 2013 to develop its messenger RNA therapeutics. The company designs mRNA chains using analogs that evade the body's immune system; the mRNA causes the creation of proteins within the cell of the patient. Moderna can design mRNA to code for almost any known protein, but the funding has come as part of the US Defense Advanced Research Projects Agency's project to develop antibody-producing drugs to fight infectious diseases and biological terrorism quickly, so Moderna's focus will likely be on mRNA therapies to fight this sort of threat. Additionally, in March 2013, Moderna signed a $240 million deal with AstraZeneca for mRNA-therapy discovery. However, not all companies are finding the development of RNA-based therapies rewarding. Marina Biotech, which develops therapeutics based on RNA interference (RNAi), sold its intellectual property for Unlocked Nucleobase Analogs—which can silence gene expression—to Arcturus Therapeutics in August 2013. The sale enables Arcturus to pursue its own RNAi therapeutics and provides some much-needed cash to Marina Biotech.
The €8 million European Union–funded VIBRANT project finished in 2013. The project consisted of ten European research groups collaborating to develop a noninvasive imaging and quantification system using quantum dots (QDs). The researchers used QDs—nanoparticles consisting of semiconductor material—to attach selectively to the insulin-producing beta cells of the pancreas and enhance the sensitivity of the magnetic-resonance imaging in use to quantify the cells. The immune system of Type 1 diabetes sufferers attacks beta cells, so the precise identification of a reduction in the number of these cells can increase the accuracy of the disease diagnosis. The scientists are now hoping to move the technology into clinical trials with the help of the project's industrial advisory board, which includes large pharmaceuticals companies such as Eli Lilly. The low cytotoxicity of QDs is also enabling researchers to find use for them in other areas of medicine, including drug delivery to targeted sites.
Regulations and Toxicity
Tellingly, BioPhotonics magazine stated in 2013 that its most popular story of 2012 was an article describing a study that found QDs were not toxic to primates in a one-year period. Although the study found no signs of illness in the rhesus monkeys that received QDs, the cadmium in the QDs stayed in the liver, spleen, and kidneys and may present a source of toxicity. The potential side effects of nanotechnology have become increasingly important to scientists as the number of biological applications rises and as some of these applications move toward commercialization. In July 2013, researchers from Brown University announced the results of a study that showed graphene could puncture and enter individual cells, in which the graphene could then disrupt normal function. The scientists hope that the study will enable engineers to alter the design of graphene so that it does not have this effect. This research and other similar studies are of great importance to companies seeking to commercialize nanotechnology products. The appropriate regulators will base laws for such products on these studies and on public attitudes about nanotechnology.
In July 2013, new EU regulation for cosmetics came into force. The regulation includes new rules for nanomaterials in cosmetic products. The EU has to authorize any nanomaterials in colorants, preservatives, and ultraviolet filters in products. All other nanomaterials that do not fall under the cosmetics regulation must undergo a European Union–level safety assessment if the European Commission has concerns about its risks. Finally, companies must list any nanomaterials present in their products as "nano" on the list of ingredients. This addition allows consumers to make a choice about whether they buy products that contain nanomaterials. Time will tell if the addition will affect the sale of these products. Further discussion about nanotechnology regulation has occurred in Europe. From June to September 2013, the European Commission held a public consultation about whether REACH—the EU regulation concerning registration, evaluation, authorization, and restriction of chemicals—should have new rules about nanomaterials. Additionally, in October 2013, Sweden produced a national action plan for the safe management of nanomaterials, which included working with other EU nations to revise REACH. In the United States, the Food and Drug Administration's Center for Drug Evaluation and Research (CDER) has also evaluated its own regulatory processes concerning nanomaterials. In October 2013, the CDER performed a review and found that its current processes are adequate at identifying potential risks to the public from nanomaterials in drugs. However, the review did note some areas for improvement, including a greater amount of nanotechnology regulatory-science research.
Look for These Developments in 2014
- Expect commercialization of nanopore-based sequencing platforms to occur in 2014. A battle may ensue between the well-publicized start-up Oxford Nanopore and the well-established Illumina if the latter decides to produce a device to compete directly with Oxford Nanopore's portable device. Illumina had a 13.5% stake in the company until Oxford Nanopore divested it for £56.4 million in November 2013.
- Gene therapy is likely to continue to grow in 2014, with UniQure leading the way. Seven months after the company formed, UniQure had its gene-therapy drug Glybera—for treating lipoprotein deficiency—approved by the European Commission in November 2012. Glybera is the first gene therapy to find approval for clinical use in either Europe or the United States. UniQure—which uses adeno-associated viruses to deliver genes—began clinical trials for its gene therapy for Sanfilippo B syndrome in November 2013. Other companies that have gene therapies nearing the final stages of testing include Amgen, Bluebird Bio, and the Children's Hospital of Philadelphia.
- Expect an increasing amount of research into therapeutics that derive from epigenetics research. A January 2013 MarketsandMarkets report predicts that the market for epigenetics—which includes RNAi and DNA methylation—will increase to $8 billion by 2017 from the current value of $2.6 billion. North America has the largest market share at 40%, with Europe following closely behind at 36%. A number of companies—including Pfizer—are researching and developing epigenetics-based therapies for cancer and chronic diseases. Additionally, epigenetics could start to move away from curative treatment to preventive treatment. Epigenetics research could expose biomarkers of aging that give an indication of a patient's current and future health. Such research could lead to the development of diagnostic tests and preemptive therapies.
- Consultations and reviews of regulations about nanotechnologies—particularly nanotechnologies in medical applications—are likely to continue in 2014. For example, a working group for the International Agency for Research on Cancer will meet in September and October 2014 to discuss the classification of some nanomaterials, depending on their likelihood of causing cancer in humans. Although public opinion and understanding of nanotechnology may influence regulation, the creation of regulation will help to improve consumer confidence in nanotechnology. Additionally, such regulation—which authorities may begin to flesh out in 2014—will increase investors' confidence in the technology.