Technologies are capable of transforming activities by making things easier or simpler to achieve. Today biotechnology has advanced in such a way that they are using the full potential for creating novel technologies for human benefits.
1. Sequencing advances and applications
Single-cell genome and transcriptome sequencing methods are generating a fresh wave of biological insights into development, cancer, and neuroscience. Genome and transcriptome sequencing require more starting material than the few picograms found in an individual cell, pushing the limits of amplification technology. Heavy amplification also propagates errors and biases, leading to uneven coverage, noise, and inaccurate quantification. Recent technical advances have helped mitigate these challenges, making single-cell sequencing an appealing way to address an expanding set of problems. Rare cell types, heterogeneous samples, phenotypes associated with mosaicism or variability, and microbes that cannot be cultured are good candidates for single-cell approaches. Single-cell sequencing can enable the discovery of clonal mutations, cryptic cell types, or transcriptional features that would be diluted or averaged out in bulk tissue studies. Single-cell genome analysis is now influencing areas as diverse as microbial ecology, cancer, prenatal genetic diagnosis and the study of human genome structure and variation
2. Biomarker analysis
Biomarker analysis uses changes in key data indicators as predictive, preventative, or personalized tools for disease states, for example, using miRNA to detect lung tumors earlier than conventional screening methods. As knowledge of biomarkers, including circulating nucleic acids markers, becomes more refined, many other examples of this pre-diagnosis are likely to emerge. The importance of early detection and appropriate therapy to outcomes cannot be underestimated.
The explosion of complex biological data on disease states has been a major factor in the development of customized, patient-specific therapeutic strategies. By using data derived from biomarker analysis, companion diagnostic approaches can identify those individual patients most likely to respond positively to specific treatments, or those patients for whom adverse drug effects are most likely. The declining cost of DNA and RNA sequencing enhances the patient-specific merits of this type of approach, and a wide range of examples of the use of biomarkers in prognostic diagnosis or treatment of diseases are now emerging.
3. CRISPR-Cas and genome editing
Clustered Regularly Interspersed Short Palindromic-Repeats (CRISPR) genome editing allows for precision genetic modifications, and when used with a suitable guide and tracer RNAs, permits unique sites of modifications to be designed at the whole genome level, as well as at the more conventional genetic element level. The power and universal utility of this tool, and indeed others such as TALENS, have been likened to the restriction endonuclease and PCR revolutions of previous decades. CRISPR tools are frequently combined with the use of the programmable DNA endonuclease Cas9 and have already been applied to more than 25 species, from viruses to rice and from zebrafish to monkeys.
The rate of CRISPR-Cas applications development is accelerating dramatically. This approach to precision-targeted genome modifications is speeding up breeding cycles in mice from 6 months to 3 weeks. It has a vast range of potential applications from gene silencing to whole genome-wide functional screening techniques and visualizing the constantly changing dynamics of genomes. CRISPR-Cas will prove especially important for disease modeling studies, has recently successfully been used by Chinese scientists in microinjected cynomolgus monkeys (Macaca fascicularis) to engineer primates with specific target mutations. Specific mutations in the Ppar-y gene, influencing metabolic regulation and in the Rag1 gene required for immune system health, have so far been investigated. While this demonstration of precisely targeted modifications has not yet led to practical applications in biomedicine, establishing the ability to do so in a primate model will prove invaluable to investigating disease states where 2,000 mutations appear to be associated with 300 conditions, developmental biology and epigenetic control of gene expression
4. Gene therapy
Hundreds of gene therapy trials have been carried out, many involving the use of adeno-associated viruses as a delivery mechanism. Vision systems provide a fruitful area for gene therapy, since there are a number of good developmental models, ranging from zebrafish to mice, and the effects of any performance changes can be relatively easily measured. Gene therapy has been successfully used to sustainably deliver improved vision, over six months, in 6/6 patients suffering from choroideremia, an X-linked progressive form of blindness, due to loss of light-harvesting cell function at the rear of the eye.
By using an adeno-associated virus delivery system, patients were administered with the CHM gene, encoding the Rab escort protein (Rep1). This approach of using adeno-associated viral delivery methods for the correction of visual system defects may prove a very promising tool for addressing macular degeneration, the major cause of blindness in developing countries in the years ahead, and has already been shown to rescue retinal degeneration with the lysophosphatidylcholine acyltransferase one gene in mice. Emerging applications for this approach extend far more widely, including the prospect of organellar gene therapy, using proteins targeted to mitochondria for example, as well as having the potential to correct heart muscle defects and to develop novel gene delivery tools to particular organs, such as electroporation to introduce brain-derived neurotrophic factor genes to enhance bionic ear cochlear implant performance in guinea pigs. The power of stem cells to overcome the loss of function, for example, associated with progressive blindness, or in the treatment of multiple sclerosis, where promising results have recently been obtained using human stem cells in mice, to overcome paralysis and a range of other nervous system communication defects, should not be underestimated.
5. 3D printing technologies
3D printing is a 30-year-old technology that is now becoming increasingly accessible to all, with entry-level equipment costs falling to as little as $600 and more than 100 different substrates now having been used to develop prototypes or products. The universal availability of computer-aided design tools and worldwide sharing of open access design elements is delivering a creativity explosion combining elements of design, composition, strength and finishing properties to produce a burgeoning number of prototypes and products combining the best of engineering and biomaterials, which can be produced by anyone, anywhere. 3D-printing will deliver massive advances in the screening of therapeutic drug candidates, for example, through the use of cell coated nanospheres, as well as tissue level surrogates, significantly reducing one of the major bottlenecks in product development pipelines to a biotechnology sector with a research and development budget of >$148 Bn annually.
The nanotechnology revolution, when allied to insights from stratified and personalized medicine, points the way towards dramatic improvements in the targeted delivery, controlled dose, and release rates of novel therapeutics. Nanoparticle biosynthesis is a highly flexible and accommodating system for the production of novel therapeutics or biotechnological tools. More than 20 nanoparticle therapeutics have now received clinical use US Food & Drug Administration approval. Even more, promising for the future are combination smart bionanomaterials, which will combine modules with different functions, so that particular target cells are identified by signal modules, recognized and bound to by separate effector modules, giving greater degrees of accuracy in treatment. Prospects for bionanomaterials will also include the use of graphene family nanomaterials, perhaps only a single molecule in thickness, of a variety of shapes and functions, not just limited to biomedicine, but with important applications in biosensing, gene delivery, advanced tissue engineering, and real-time imaging
Flexibility and potential for imaginative new products to be created are demonstrated by advances in origami DNA, whereby long DNA strands can be shaped into almost any three-dimensional nanostructure. This has applications in biocomputing, using DNA based robots to act as logic gates, channels, and components of artificial machines, which has recently been extended to living cockroaches (Blaberus discoidalis) to control cell targeting.
7. Wearable devices
The potential for wearable devices to be used in routine telehealth is also shown by recent plans for Apple to expand into the health sector, described by CEO Tim Cook as ‘primed to explode’. The much-rumored iWatch may have the blood-sugar level and nutrition monitoring functions, as well as tracking activities, and remotely send on a range of other physiological functions such as blood pressure, heart rate, temperature, hydration, and antioxidant status. Apple is believed to have assembled high powered teams of biomedical scientists, engineers, software, and hardware gurus from a range of telehealth and sensor technology companies, including Vital Connect, Sano Intelligence, and O2 MedTech, further telehealth wearable device developments are inevitable.
8. Citizen science
Novel applications of the technology are not just limited to industrial or research-led processes. Individual citizens can become involved in the testing or analysis of biotechnological data through ‘Citizen Science’ initiatives. While mobile phone apps are enabling the public to record and report incidences of unusual plant diseases, which can be identified and mapped remotely, citizens can also become directly involved in the analysis of original data generated through large, interdisciplinary projects.
Such initiatives frequently involve members of the public in the analysis of genomic or microarray data, to assist in mapping or three-dimensional modeling projects. The ubiquity of powerful computing tools in our everyday lives allows us all to contribute as Citizen Scientists to the advancement of knowledge- and have some fun in the process.