Read | Write | Edit | Genomes Redefining breakthroughs in Research & Discovery

BY: Dr Tani Agarwal - 17 May-2021

Ticking more new right boxes every day, Genomics research is clearly making strides. Deep sequencing of the genome, which was once unfathomable for humankind, has now become staple for myriad applications across laboratories. At Premas Life Sciences, we are facilitating the whole process from scratch – with game-changing technologies assisting the Indian researchers at the frontlines.

 

Reading the Genome

Advanced genomics tools and computational innovation have led deep-sequencing to the center stage of public health and healthcare. Rapid genome sequencing of the SARS-CoV-2 accelerated prediction and design of vaccine targets within a couple of days after the sequence was reported. Reading of the genome which includes not just genome sequencing, but identifying methylation sites and epigenetic markers is accessible to us through various whole genome seq, whole exome seq or targeted panels. As clinical genomics hinges on the accurate reading of the genomic footprints of disease markers and therapeutic targets, advanced technologies and customizable tools and gene panels have given birth to precision medicine.

Interestingly, over the last two decades, reading or sequencing the genome has become not just easier and faster but also affordable. Today, the cost of sequencing a whole genome is nearly $1000 as compared to $100,000, just a decade back. With the integration of artificial intelligence and machine learning tools, genomic data is being combined with evidence from literature to find meaningful relationships around the target genes to meet clinical needs. 

 

Writing the Genome

Move over genetically modified species, whereby one or a few genes are genetically engineered. One can now write an entire new gene. As profound as it sounds, writing genomes or parts of it has been made possible through neat and innovative technologies in cloning methodologies and automation thereof. Researchers can now explore endless possibilities by combining genetic traits and features from different species and organisms. Be it drought and pest resistant crop seeds, or rapid development of vaccines against COVID-19 or other infectious diseases, to lab-cultivated meatless-meats and dairy, with synthetic biology the possibilities are expansive.  While a do-it-yourself (DIY) gene writing/creating synthetic genes may seem fantasy-like, but the same has been realized with long DNA syntheses backed by amalgamation of cutting-edge enzyme chemistry and automation. Hail— the gene Printer platform BioXp 3250 from Codex DNA. Imagine creating tens of long synthetic gene constructs in your own lab within hours, without having to do tedious plasmid preps or dealing with contamination or low yields. Yes, this can all be achieved through the world’s only gene printer created by Codex DNA.  This can potentially accelerate advances in the fields of personalized medicine, antibody engineering, vaccine development, biologics, and more. 

 

Editing the genome

Genome editing is the procedure whereby the planned manipulation of a gene/set of genes is performed using molecular biology approaches to achieve desirable molecular properties in a cell. Analogous to a film reel that can be edited with a cut here and a paste there; the genome is also being explored in newer ways through genome editing.  While Bacterial genome editing is most common, gene manipulation is easily performed in-vitro in human and plant stem cells. With plethora of available tools for editing the genomic structure combined with excellent research in enzyme chemistry has pushed the research gears ahead. Moreover, access to genome editing tools like CRISPR, TALENs, ZFNs and MAGE is available for close to free through the non-profit Addgene.org. 


Genome editing through Crispr-Cas9 system is the most popular tool that genome engineers are using now adays to create new paradigms in diagnostics, therapeutic interventions as well as GM foods etc.  This has poised a revolutionary ecosystem for developing new molecular devices as well as game changing immunotherapies like CARTs and genome-edited crops. The recent approval from FDA (as well as under review for accelerated approval from EMA) of Zolgensma (Onasemnogene Abeparvovec-xioi) which is a gene replacement therapy for Spinal Muscular atrophy for pediatric patients, is a breakthrough development for gene therapy researchers. Although slated as the most expensive drug (priced at INR 18Cr for one dose); Zolgensma has paved way for more rapid advancement of gene-therapy based treatments for other diseased conditions.


While fancified memes have sketched a comic picture of a genome editing clinic similar to a salon where customized styles/designs are created on demand. So next time round, designer babies may just not be so difficult to imagine.
Above all, the future of genome engineering lies in the enabling to create or write entire new genes and genomes to the benefit of mankind. This will require researchers to interpret the genome language well through culmination of the three steps- read, edit and write the genome.

References
1) Chari, R., & Church, G. M. (2017). Beyond editing to writing large genomes. Nature reviews. Genetics, 18(12), 749–760. 
2) Menz, J., Modrzejewski, D., Hartung, F., Wilhelm, R., & Sprink, T. (2020). Genome Edited Crops Touch the Market: A View on the Global Development and Regulatory Environment. Frontiers in plant science, 11, 586027. 
3) Stevens, D., Claborn, M. K., Gildon, B. L., Kessler, T. L., & Walker, C. (2020). Onasemnogene Abeparvovec-xioi: Gene Therapy for Spinal Muscular Atrophy. The Annals of pharmacotherapy, 54(10), 1001–1009.
4) https://www.genome.gov/about-genomics/fact-sheets/Sequencing-Human-Genome-cost


About Author 

Dr Tani Agarwal
Email - tani@premaslifesciences.com


 

*This story is published by VOH team*

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