Research and Development
The last few decades brought tremendous development in biology and medicine, however, it still takes way too long for basic scientific results to appear in the daily practice. It is an extremely important task to convert the greatest available scientific achievements into every-days practice!
However, we know that this is not enough, and that is why we keep an eye on adaptable cutting edge technologies and try to envisage the future. Here are some research opportunities that we find crucial for future biotechnology and medical practice.
Gene therapy will be the technology that enables the efficient and safe delivery of genes into patient’s cells. It already has a great history, as the first attempt happened in 1980. However, early clinical failures halted the research for a longer period. The death of a patient due to severe immune reaction, and observation of cancer as side-effect of the procedure set back trials and horrified public.
Only since 2006 gene therapy has been gaining increased attention. Safety was improved a lot and Ventures, Big Pharma companies also started to invest again. This is nicely demonstrated by the 3.5x increase in the number of gene therapy companies in the last four years (69 to 255; ARM data).
Oncology and rare diseases dominate the current field, other diseases comprise about one third of cases. As vehicle, viral delivery is used in 2/3s of the trials, within this Adeno-associated viruses (AAVs) are followed by Lentivirus, Adenovirus, Retrovirus and Vaccinia virus.
Disadvantages of rAAVs
Although AAVs are less immunogenic than other viruses, different layers of the host immune system can be triggered. A major difficulty is the effective but non-immunogenic dose, since most of the patients have previous AAV infections, so the host system usually had already developped an immune response against AAV virus particles. Another disadvantage is cargo size, that is really limited to 5 kb at the maximum in AAV vectors.
AAVs have single stranded DNA genomes, thus it has to be converted to dsDNA first and than can the integration happen. During the second strand synthesis, errors can form which leads to inefficient transgene expression or other problems. The viral DNA preferentially integrates into active genes that can be a major disadvantage itself. Additionally, the integration happens through non-homologous end-joining (NHEJ) frequently associated with chromosomal rearrangements and deletions of large segments of the DNA .
So, the currently used most popular vector has basic weaknesses, but the other tools are not different in this sense. The major difficulties with all viral delivery vehicles are similar: immunogenicity and cytotoxicity, limited cargo size and insertional mutagenesis.
It is obvious that current delivery tools are quite far from ideal and there is great room for further developments or completely new approaches. There is a great demand for highly efficient and safe gene delivery.
3D printing (additive manufacturing) combined with biocompatible plastics in biology and medicine
3D printing is a revolutionary technology which has already appeared in medicine and biology. There are four core uses of 3D printing in the medical field that are associated with recent innovations: creating tissues and organoids, surgical tools, patient-specific surgical models and custom-made prosthetics. Some interesting current results:
Tissue and organ bioprinting
For tissue building, first a scaffold is built, and subsequently cells are placed on the surface. 3D printing can be used for making both the scaffold and the distribution of cells. Bioprinting enables precise placement of high-density cells in desired locations. So, native tissues can be mimiced arranging multiple types of cells in an ordered structure. For e.g. 3D bioprinting has been used for producing cartilage tissues by printing chondrocytes into hydrogel scaffolds. Current research also focuses on developing portions of skin to help burn victims.
Printed surgical tools
It is not possible to completely prevent the transfer of infectious agents (e.g. MRSA) by surgical tools from one patient to the other. Traditional surgical tools are too expensive to be used only once. However, 3D printed objects are cheap enough, could be used for one patient only, and complete recycling is possible.