Nanotechnology is a “catch-all”¯ description of activities at the level of atoms and molecules that are used in the real world. It describes materials, systems and devices with characteristic dimensions in the range 1-100 nanometer (nm). One nanometre is a billionth of a meter, that is, about 1/80,000 of the diameter of a human hair, or 10 times the diameter of a hydrogen atom.
Nanoscience is not a new discipline but a new agenda that different disciplines can contribute to. It is the study of novel phenomena and properties of materials that occur at extremely small length scales ”“ on the scale of atoms and molecules. Nanotechnology is the application of nanoscale science, engineering and technology to produce novel materials and devices, including biological and medical applications.
Nanotechnology has opened up new possibilities and it has spawned a spread of new terminology – a kind of nanospeak to the uninitiated.
Another feature of nanotechnology is that it is the one area of research and development that is multidisciplinary.
Research at the nanoscale is unified by the need to share knowledge on tools and techniques, as well as information on the physics affecting atomic and molecular interactions in this new realm. Materials scientists, mechanical and electronic engineers and medical researchers are now forming teams with biologists, physicists and chemists.
Nanoscale science and technology contributes controlled component design and fabrication on atomic and molecular scales. Nano-related research and development unites results and processes from biotechnology and genetic engineering with chemistry, physics, electronics and materials science with the aim of manufacturing cost-effective innovative products. Nanotechnology has been recognized by leading industrialized countries and it has gained the potential key economic significance in the 21st century.
Nanotechnology contributes controlled component design and fabrication on atomic and molecular scales. It unites findings and processes from biotechnology and genetic engineering with chemistry, physics, electronics and materials science with the aim of manufacturing cost-effective innovative products. Increasing miniaturization is accompanied by an irrevocable increase in the importance of mastering and reliably implementing extreme nanoscale technologies in a mass production manufacturing environment. General examples of nanotechnology products include some magnetic memory devices, optical, protective and decorative layers, some sunscreens and many cosmetics.
Gene therapy is the transfer of genetic information into cells and tissues to achieve some desired effect. In humans, gene therapy is typically used to treat or compensate for a genetic mutation in the cellular genetic machinery or to increase the production of a certain protein. Gene therapy is used to treat systemic conditions and it has been quite difficult because it requires the transformation of large areas of human tissue in the body that need to last the lifetime of the patient. For the treatment of spinal disorders however, we only need to transfer the genes to small portions of the spinal tissues and this only needs to last for a short period of time (such as for spinal fusion).
Gene therapy involves replacing, removing, introducing, or otherwise altering genes in order to prevent or treat disease. Usually researchers corrects faulty genes by adding normal genes into the genome, replacing abnormal genes, selectively mutating abnormal genes, or by altering the degree to with a gene is turned “on”¯ or “off.”¯
As the genetic and molecular basis for a multiplicity of diseases has become clear, the promise of gene therapy continues to grow. Although initial efforts in gene therapy focused on delivering a normal copy of a missing or defective gene, current programs are applying gene delivery technology across a broader spectrum of disease conditions. Gene delivery is now being used to:
1. Replace missing or defective genes;
2. Deliver genes that catalyze the destruction of cancer cells or cause cancer cells to revert back to normal tissue;
3. Deliver viral or bacterial genes as a form of vaccination;
4. Deliver genes that promote the growth of new tissue or stimulate regeneration of damaged tissue.
Gene therapy has grown out of the science of genetics or how heredity works. Scientists know that life begins in a cell, the basic building block of all multicellular organisms. Humans are made up of trillions of cells, each performing a specific function. Within the cell’s nucleus (the center part of a cell that regulates its chemical functions) are pairs of chromosomes. These threadlike structures are made up of a single molecule of DNA (deoxyribonucleic acid), which carries the blueprint of life in the form of codes, or genes, that determine inherited characteristics.
Scientists have known how to manipulate a gene’s structure in the laboratory since the early 1970s through a process called gene linkup. The process involves removing a fragment of DNA containing the specific genetic sequence desired, then inserting it into the DNA of another gene. The resultant product is called recombinant DNA and the process is genetic engineering.
There are basically two types of gene therapy. Germ-line gene therapy introduces genes into reproductive cells (sperm and eggs) or someday possibly into embryos in hopes of correcting genetic abnormalities that could be passed on to future generations. Most of the current work in applying gene therapy, however, has been in the realm of somatic gene therapy. In this type of gene therapy, therapeutic genes are inserted into tissue or cells to produce a naturally occurring protein or substance that is lacking or not functioning correctly in an individual patient.
The potential scope of gene therapy is enormous. More than 4,200 diseases have been identified as resulting directly from abnormal genes, and countless others that may be partially influenced by a person’s genetic makeup. Initial research has concentrated on developing gene therapies for diseases whose genetic origins have been established and for other diseases that can be cured or improved by substances genes produce.
Although great strides have been made in gene therapy in a relatively short time, its potential usefulness has been limited by lack of scientific data concerning the multitude of functions that genes control in the human body. It is now known that the vast majority of genetic material does not store information for the creation of proteins, but rather is involved in the control and regulation of gene expression, and is, thus, much more difficult to interpret.
Even so, each individual cell in the body carries thousands of genes coding for proteins, with some estimates as high as 150,000 genes. For gene therapy to advance to its full potential, scientists must discover the biological role of each of these individual genes and where the base pairs that make them up are located on DNA.
Gene therapy seems quite simple in its concept: supply the human body with a gene that can correct a biologicalĀ malfunction that causes a disease. However, there are many obstacles and some distinct questions concerning the viability of gene therapy. For example, viral vectors must be carefully controlled lest they infect the patient with a viral disease. Some vectors, like retroviruses, also can enter cells functioning properly and interfere with the natural biological processes, possibly leading to other diseases. Other viral vectors, like the adenoviruses, often are recognized and destroyed by the immune system so their therapeutic effects are short-lived. Maintaining gene expression so it performs its role properly after vector delivery is difficult. As a result, some therapies need to be repeated often to provide long-lasting benefits.
One of the most pressing issues, however, is gene regulation. Genes work in concert to regulate their functioning. In other words, several genes may play a part in turning other genes on and off. For example, certain genes work together to stimulate cell division and growth, but if these are not regulated, the inserted genes could cause tumor formation and cancer. Another difficulty is learning how to make the gene go into action only when needed. For the best and safest therapeutic effort, a specific gene should turn on, for example, when certain levels of a protein or enzyme are low and must be replaced. But the gene also should remain dormant when not needed to ensure it doesn’t oversupply a substance and disturb the body’s delicate chemical makeup.
While gene therapy stays a revolutionary approach to treating disease, ethical concerns over its use and ramifications have been expressed by scientists and lay people alike. Since much needs to be learned about how these genes actually work and their long-term effect, is it ethical to test these therapies on humans, where they could have a disastrous result? As with most clinical trials concerning new therapies, including many drugs, the patients participating in these studies usually have not responded to more established therapies and often are so ill the novel therapy is their only hope for long-term survival.
Another questionable outgrowth of gene therapy is that scientists could possibly manipulate genes to genetically control traits in human offspring that are not health related. The Human Genome Project (Nevin, Norman. “What Has Happened to Gene Therapy?”¯ European Journal of Pediatrics (2000): S240-S242), which plays such an integral role for the future of gene therapy, also has social repercussions. Some of these concerns can be traced back to the eugenics movement popular in the first half of the twentieth century. This genetic “philosophy”¯ was a societal movement that encouraged people with “positive”¯ traits to reproduce while those with less desirable traits were sanctioned from having children. Eugenics was used to pass strict immigration laws in the United States, barring less suitable people from entering the country lest they reduce the quality of the country’s collective gene pool.
Gene therapy and its benefits:
A primary benefit of gene therapy is the ability to correct the underlying cause of genetic diseases. To date, the majority of therapeutics available for diseases such as cystic fibrosis, hemophilia and Gaucher’s disease only palliate disease symptoms. The delivery of functional copies of the genes involved in these diseases provides a mechanism through which the disease may be corrected at the molecular level. Gene therapy also holds the potential to provide patient-friendly treatment regimens for a variety of diseases. Today, patients with hemophilia, diabetes and other diseases that are treated by the administration of therapeutic proteins must take daily or weekly injections in order to manage their disease. This is because proteins exist in the blood stream for a limited period of time before they are degraded or eliminated. Because DNA is more stable and functions inside the cell, the delivery of therapeutic genes may result in longer-term expression of therapeutic proteins. Dosing regimens for gene therapy products are likely to require treatment every few weeks or every few months.
The combination of many new techniques is opening the door to the resolution of biological questions, such as the functioning of the immune system, that would have been intractable even a few years ago. This new knowledge, together with the deciphering of the human and other animal and plant genomes is plunging us into the thick of a biomedical revolution. The result is an explosion of entirely new industries across the healthcare, medicine, food and nutrition, environmental management, chemical synthesis, agriculture and non-food agricultural sectors.
Nanotechnology allied with biotechnology are the underpinning technologies pushing the rapid advances in genomics, combinatorial chemistry, drug discovery, gene sequencing and bioinformatics and their applications.
Gene therapy may potentially ameliorate many disorders in the central nervous system (CNS). The success of gene therapy relies upon cell-specific gene transfer, a procedure that would ensure therapeutic efficacy in the cells of interest while limiting side effects such as immune, inflammatory and cytotoxic responses, which are caused by the expression of exogenous genes in non-target cells. This talk will introduce our work in exploring various approaches for targeted gene transfer in neurons. For transcriptional targeting, hybrid promoters containing a neuron-specific promoter and a viral transcriptional regulatory element have been constructed and tested. For transductional targeting, recombinant protein- or peptide-based, nonviral vectors have been developed for targeted entry of the vectors into neurons through specific ligand-receptor interaction and receptor-mediated endocytosis. We have also developed methods to target and transduce neurons in remote CNS regions through axonal transport. Our continued research in this area is aimed at developing an effective means for neuron-specific transgene expression that is required for gene therapy of neurological disorders, as well as functional genomics research of the nervous system.
Although gene therapy testing in humans has advanced rapidly, many questions surround its use. For example, some scientists are concerned that the therapeutic genes themselves may cause disease. Others fear that germ-line gene therapy may be used to control human development in ways not connected with disease, like intelligence or appearance.
It is impossible to disclaim that many accomplishments were achieved in Nanothechnology and Gene therapy in particular butĀ still it suffers from the problems that other interdisciplinary research areas face:
1. A lack of understanding of biological systems will slow many developments.
2. Oversimplification by biotech companies including university spin-offs. Pressure for universities to generate income through tech transfer means there are fewer people to take an independent view of some of the claims about progress.
3. Links with industry: It was felt that science needs to have close links with industry to turn nanoscience into nanotechnology. These close links tend to worry the public.
4. Nanoscience technology is becoming “big science”¯ with large infrastructure requirements. This requires large amounts of money to uphold the infrastructure and enable continuity in staffing; platform grants will help.
5. Community claims that nanotechnology will be very big. With any technology there will be the fear that possession of the technology gives power to a small number of people.