Nanotechnology an Enabler for Biotech

- Summary -

Global Emerging Technology Institute (GETI)

Several countries are very actively supporting the application of nanotechnology for use in biotechnology. This "nanobio" effort can have a very significant impact on a sector that is struggling to produce innovative technologies that aide in the development of drug discovery tools and creation of large-market drugs. The nanobio focus should increase as the search for breakthroughs becomes more desperate and the funding sources become more demanding. These includes both pharmaceutical companies that often partner with biotech firms in order to help fund R&D (often becoming the exclusive licensee) and professional investors. Though the U.S. biotech industry still is the clear leader in innovation, foreign research initiatives and government support in nanobio may serve to close the gap. This may be due to the fact that though drug companies, regardless of the geographical location, all have relatively dry pipelines of new drugs, firms in Japan and Europe, for example, are even dryer than in the U.S. As a result, foreign companies, including start-ups, are attempting to develop expertise in key niche areas and are being strongly supported by the public sector via the development of industry-run led, government organized research consortia that is coupled with related activity taking place in government or quasi-government labs and universities.

Researchers at the Biological Information Research Center at Japan's Advanced Industrial Science & Technology office (AIST) have developed a system to help proteomics identify proteins from intracellular compartments or in macromolecular complexes. This system is a combination of liquid chromatography (LC) and electrospray tandem mass spectrometry (MS/MS) and direct nano flow LC-MS/MS (DNLC-MS/MS). The advantage of this system is that it does not need a pre-separation of the proteins, which always leads to losses in proteins, thus it produces a far higher yield. The other advantage the system possesses is that the time required for the analyses is much shorter (1 hour instead of 2 weeks). The system can effectively identify 100-150 proteins in a single run. In order to understand protein-protein interactions, human cDNA is used as a bait and expressed in human cells. The expressed proteins, and their associated "ligands" are purified from the cell lysate using anti-tag affinity beads, and identified using the DNLC-MS/MS system. This can be used to analyze groups of degrading proteins, or identify the molecular function of a protein in case of a disease-related gene.

At Tokyo Women's Medical University, researchers have proposed a method of cultivating cells on a dish surface, in which the removal of the resulting layer respects the integrity of the deposited extra cellular matrix (ECM). The technique consists of the cultivation of cells on a very thin surface (20-30 nm) of a temperature-responsive polymer, poly (N-isopropylacrylamide) (PIPAAm), covalently attached to the surface of the cultivating plate. Decreasing the temperature after the cells have proliferated to confluency allows the cells to detach from the surface of the PIPAAm, with intact cell-to-cell junctions and ECM. The advantage of preserving the ECM is that it is possible to layer several cell sheets so as to have a stratified tissue that can be used to replace a pathological one. This has already application in regenerative medicine, as corneal cell sheets have already been transplanted in patients, and cardiomyocytes layers can replace damaged tissues in case of infarctus.

In France, a nanobio project was initiated in Grenoble in 2002 by the CEA-Grenoble and the NattBio project based in Toulouse. This project was aimed at developing competencies in nanobio-technologies in order to support more advanced research in this emerging field. Since June 2002 both projects have been affiliated with European NanoToLife, which seeks support the creation of a cluster of competences in nanotechnologies, including nanobio. These programs have supported the development of a number of start-up companies including: Apibio (established in 2001), an offshoot from CEA-Leti; Biomerieux, a company possessing 50 patents that focuses on the DNA chip market; and ProteineXpert (established in 2000) concentrating on high throughput production of proteins using a proprietary process. Other companies, such as Nanobiogene in Besancon, are engaged in the development and production of microfluidic spottage modules for genomic and proteomic related research.

In Switzerland, nanobio is being supported through several initiatives, including those under the umbrella of the "TOP NANO 21" (2000-2003) initiative. The National Center of Competence in Research on Nanoscale Science NCCR (2001-2011) for interdisciplinary basic research has a strong emphasis on the life sciences and medicine. Within the NCCR, the University of Basel plays a leading role, maintaining a network of university institutes, research institutes and industrial partners. It is currently supporting 10 projects, a number of which are focused on nanobio including studies that seek a cure/therapy for the prevention of arthritis, measuring the pathological changes of cartilage in the nanometer range (are detectable when they cannot be measured on the millimeter scale). Other projects include ones on arteriosclerosis (inflammation and deposits can be characterized by AFM), the development of a Nanomechanical Olfactory SEnsor (NOSE) that can detect characteristic substances in exhaled air and body fluid (as for diabetes) and the design of nanoparticles to be used as drug delivery systems.