Engineering the Cure: Advancement in Molecular Biology is building better drugs

Molecular biology holds the capacity to impact nearly every facet of drug research, development, and utilization.   

The elementary molecular biology methods are used in basic research to cultivate bacterial cell lines for recombinant protein synthesis. Hence understanding the c0ncept behind target gene and method to the extraction of gene of interest (GOI) from the genome, clone GOI into an expression vector, create bacterial strain, identify positive clones, cultivate recombinant cells, and stimulate the synthesis of the target protein are crucial. Methods like Western blot, ELISA, and SDS-PAGE are employed to identify and measure the active recombinant protein. Many of the aspirants develop these skill while completing graduate degrees and are useful in R&D units across Biopharma sector. These techniques are often used in the biopharmaceutical development process to check the product quality.   

Traditional methods of molecular biology use in drug discovery research involve tedious manual operations that do not offer sufficiently accurate and precise quantitation, or the desired turnaround time and sample throughput. In order to meet industrial standards and requirements, a fully automated, high throughput instrument for capillary electrophoresis (CE) protein separation and subsequent western blot analysis has been developed. This high throughput technology is being used in vaccine development, analysis of monoclonal antibody and peptide charge heterogeneity, biomarker detection, characterization of endogenous protein in cell lysates and industrial biopharmaceutical protein characterization. CE-based western blot are commonly for studies of medicinal proteins and vaccines. Molecular biologist should have this skill added to their continuous learning process. This technology at industrial level is being used as a best practice to quantitatively monitoring the clearance of a specific host cell proteins. Likewise, CE western technology has been more beneficial to evaluate contaminants of a biopharmaceutical Fusion-Fc protein during its purification process in comparison to traditional slab gel western blot. Such technologies are expedient to the quality by design (QbD) concept implementation in  bipharma landscape, e.g. a biopharmaceutical protein in cell culture harvest samples was separated based on size using an automated CE western system to measure directly its two critical quality attributes namely a total protein expression or titer was measured using a primary antibody and a secondary antibody coupled with HRP to measure a total protein expression or titer and an HRP-conjugated primary antibody to measure manufacturing consistency in quantifying the relative distribution of the main protein isoforms. Therefore an innovative strategy based on automated CE western blot backs as a prospective analytical technique for sophisticated process control in the production of therapeutic proteins. [1] It is wise to advance the laboratory skill with CE based technologies. Promega, Agile Technologies, Lumex Instruments, Sebia, SCIEX, Helena Laboratories, Thermo Fisher Scientific, PerkinElmer, and BiOptic Inc. are the leading players in the capillary electrophoresis (CE) instruments market. To meet the needs of many industries, they provide a broad range of goods and solutions. To keep a competitive advantage in the market, they also frequently offer extensive customer support services and concentrate on ongoing product innovation. The market for capillary electrophoresis was estimated to be worth US$ 325.3 million in 2024 and is projected to grow at a compound annual growth rate (CAGR) of 4.3% from 2024 to 2031, reaching US$ 438.8 million. [2] 

Understanding the role of genetics in disease has become a central part of medical research while molecular biology based techniques are common tools used to study the functional genomics. Genomic analysis techniques such as Next-Generation Seqencing (NSG), microarray, RNA-Seqencing (RNA-Seq.), In-situ hybridization (ISH), quantitative real time polymerase chain reaction (qRT-PCR) are being used to look at the gene expression. When compare NSG with qPCR, qPCR can only identify known sequences, yet both provide extremely sensitive and trustworthy variant detection. Nevertheless NGS is an approach that does not rely on past knowledge of sequence information and is free of assumptions. With NGS, researchers find new genes with greater discovery power and measure rare transcripts and variations with greater sensitivity. In 2023, whole genome sequencing has cost less than $1 per GB thanks to NSG technology. [3] The leading innovative systems in the market include PromethION (Oxford Nanopore Technologies), Ion Torrent Genexus Dx Integrated Sequencer (Thermo Fisher), iSeq 100 (Illumnia), and Ion GeneSstudio S5 System (Thermo Fisher). The next generation sequencing market is expected to develop at a compound annual growth rate (CAGR) of 15.7% from 2022 to 2027, from an estimated USD 13 billion in sales in 2022 to USD 27 billion by 2027. [4]

Drug efficacy inconsistency caused by the gene polymorphism across population. Breakthrough gene editing technologies in molecular biology, now it is possible to restore or reverse genetic abnormalities that lead to disease in an individual. This technology enables restoring essential protein function and allowing the body to function correctly this has open the door to precision medicine (PM) in the market. For many scientists, CRISPR-Cas9 is the preferred gene editing tool over ZFNs and TALENS, and it has the potential to lead to revolutionary breakthroughs in biology, medicine. When compared to alternative methods, CRISPR-Cas9 seems to be more rapid, accurate, effective, and economical. [5] The first treatment using CRISPR/Cas9, a kind of genome editing technology, to receive FDA approval is called Casgevy. Thermofisher Scientific, Inc. (US), Merck KGaA (Germany), Agilent Technologies, Inc. (US), Genscript Biotech Corporation (China), CRISPR Therapeutics AG (Switzerland), Editas Medicine (US), and dozens of other notable businesses are prominent players in the CRISPR market. According to revenue estimates, the global CRISPER market will be valued USD 3.4 billion in 2023 and is expected to rise at a compound annual growth rate (CAGR) of 15.6% from 2023 to 2028, when it reaches USD 7.1 billion. [6] 

New technologies such as CRISPR-Cas9 gene editing opens doors for potential treatments for various genetic disorders, NGS offers a potent tool for understanding the genetic basis of diseases and helps in accurate drug discovery, and CE-western blot offers significant advantages in quality control. In conclusion, the ongoing expansion of the markets for CRISPR, NGS, and CE highlights the enormous potential that molecular biology has to shape healthcare in the future.

References: 

1. Mishra M, Tiwari S, Gomes AV. Protein purification and analysis: next generation Western blotting techniques. Expert Rev Proteomics. 2017 Nov;14(11):1037-1053. doi: 10.1080/14789450.2017.1388167. Epub 2017 Oct 13. PMID: 28974114; PMCID: PMC6810642.

2. AST 5339 Market Research Report, Markets & Markets Published ON April 2023, Accessed on March 2024. URL : https://www.marketsandmarkets.com/Market Reports/electrophoresis-market-434.html

Complete Genomics' DNBSEQ-T20x2RS* Named "Next Generation Sequencing Solution of the Year" by 2023 BioTech Breakthrough Awards Program, PR Newswire published on Nov. 2023 Accessed on March 2024. URL: https://www.prnewswire.com/news-releases/complete genomics-dnbseq-t20x2rs-named-next-generation-sequencing-solution-of-the-year-by-2023 biotech-breakthrough-awards-program-301981211.html

1. BT 6746 Market Research Report, Markets & Markets Published on June 2023, Accessed on March 2024. URL: https://www.marketsandmarkets.com/Market-Reports/crispr-technology market-134401204.html

2. Semiz, S., Aka, P.C. Precision medicine in the era of CRISPR-Cas9: evidence from Bosnia and Herzegovina. Palgrave Commun 5, 134 (2019). https://doi.org/10.1057/s41599-019-0346-2.

3. BT 2697 Next Generation Sequencing Market, Markets & Markets Published on Jan 2023, Accessed on March 2024. URL: https://www.marketsandmarkets.com/Market-Reports/next generation-sequencing-ngs-technologies-market-546.html

About the Author:

Shruti Talashi

Ms.  Shruti  Talashi  boasts a dual mastery of lab research and writing.  Her doctoral study outcome as M.Phil in biomedical science while studying  breast cancer and an extraordinary masters degrees dissertation work on  exploring role of Gal-lectin in cancer metastasis fuels her extensive  research interests. She has gained few publication in journals. Bridging the  science-public gap is her passion, aided by expertise in diverse techniques.  From oncology to antibiotic/drugs production, she's led and managed complex  projects, even clinical trials. Now, as a freelance Content Coordinator for  Sinoexpo Pharmasource.com, her industry knowledge shines through valuable  insights on cutting-edge topics like GMP, QbD, and biofoundry.