Genomics research has greatly progressed over the last century, from the discovery of DNA in the late 1860s to the complete mapping of the human genome to modern-day advances such as leveraging genomics in disease control.
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Recently, the field of genomics has witnessed many advances in technology that have allowed scientists to sequence genomes at an unprecedented rate and a fraction of the cost. The rich information revealed by a person’s genomic profile has incredible value in scientific research as it helps scientists develop novel therapeutics that are more effective. Here, we discuss how technology has transformed genomics research.
ZFN, TALEN, and CRISPR–Cas9
Many technologies have helped to further genomics research. However, arguably, ZFN, TALEN, and CRISPR-Cas9 technology have been three of the most important technologies in this field.
Zinc-finger nucleases (ZFNs) are engineered DNA-binding proteins or DNA cleavage reagents, that facilitate targeting editing by forming double-strand breaks in DNA at specific locations. ZFNs, therefore, have been developed into gene-editing tools that are useful for inducing targeted mutagenesis and carrying out targeted gene replacement at high frequencies. It is considered that the birth of ZFNs gave researchers tools with unprecedented capabilities to perform genetic manipulation.
Transcription Activator-Like Effector Nucleases (TALEN) was established in 2011. Scientists studying Xanthomonas bacteria found that the microbes were secreting effector proteins (transcription activator-like effectors, TALEs) onto the cytoplasm of plant cells, increasing their susceptibility to the bacteria. Under further investigation, the scientists discovered the action mechanisms of the effector protein were able to perform DNA binding and induce gene expression by mimicking the eukaryotic transcription factors. Instantly, it was clear that these effector proteins (TALEs) had great potential in the field of genomics.
After a few more years of work, researchers added a nuclear localization signal, half-repeat, N-terminal domain, resulting in ‘TALENs’. TALENs are artificial restriction enzymes, able to recognize specific sequences within the genome and produce double-strand breaks.
At around the same time, other groups of scientists were working on developing CRISPR-Cas9 technology, possibly the most famous genomic tool due in part to the controversial conversations it has sparked. The technology is based on two key molecules, the first is the enzyme Cas9 that acts like a pair of ‘molecular scissors’, cutting into the two strands of DNA at a predetermined location. The second is a piece of guide RNA (gRNA) that guides the enzyme to the correct part of the genomic sequence. CRISPR-Cas9 technology allows scientists to remove, add, or alter sections of the genome.
In vitro studies have already demonstrated that CRISPR-Cas9 technology has the potential to correct genetic defects such as cystic fibrosis, cataracts, and Fanconi anemia. The technology has also been used in early-stage clinical trials as a potential cancer therapy. It has also been considered as a potential tool to prevent the spread of Lyme disease, malaria, and HIV. The technology has aroused much excitement due to its potential applications across medicine and healthcare.
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HudsonAlpha Institute: leveraging technology in genomics research
The HudsonAlpha Institute for Biotechnology in the US is one of the global leaders in terms of genomics research. To date, work that has taken place at the institute has resulted in the development of important new therapeutics and has played a critical role in major projects including the Human Genome Project, The Cancer Genome Atlas (TCGA), and the Encyclopedia of DNA Elements (ENCODE) Project, to name a few.
Technological advancement has been at the center of HudsonAlpha’s excellence. The work undertaken at the institute is data-intensive, with significant demands in terms of data storage, manipulation, and analysis. Early on, the team at HudsonAlpha adopted cloud technology and hyper-converged infrastructure. They also leveraged composable infrastructure, which combines compute, storage, and network fabric into one resource. This amalgamation of hyper-converged and composable infrastructure has reduced the re-provisioning time from four days to under two hours as well as reduced costs.
Speed is important in research, it allows scientists to speed up the methodology and analysis and arrive at the conclusion. In genomics research, this means that scientists are able to generate genomic profiles faster, which contributes to speeding up the process of developing new therapeutics based on this research.
Genomics research and COVID-19
Genomic sequencing played an important role in controlling the COVID-19 pandemic. It allowed researchers to quickly understand the virus, how it spread, and how it affected the body. This helped us to develop preventative strategies and establish vaccines. Without genomics, the rapid roll-out of vaccination programs that was observed globally would not have been possible. The pandemic highlighted the importance of genomics, and it will likely dictate how genomics technology moves forward.
There is now a focus on preparing for the emergence of the next pathogen with pandemic potential. Rapid screening programs and testing will be essential to pandemic strategies going forward, and genomics technology will likely develop to enhance that in any way possible.
- Becker, S. and Boch, J., 2021. TALE and TALEN genome editing technologies. Gene and Genome Editing, 2, p.100007. https://www.sciencedirect.com/science/article/pii/S2666388021000071
- Carroll, D., 2011. Genome Engineering With Zinc-Finger Nucleases. Genetics, 188(4), pp.773-782. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3176093/
- Li, H., Yang, Y., Hong, W., Huang, M., Wu, M. and Zhao, X., 2020. Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects. Signal Transduction and Targeted Therapy, 5(1). https://www.nature.com/articles/s41392-019-0089-y