Fueling Precision Medicine: From Sequence to Therapeutics

We are on the precipice of the next major shift in science as it relates to medicine. The 20th Century saw an explosion of technological advances that reshaped modern life completely. Today, the surge of discoveries and development continues particularly in biology. It is very possible that our counter arts in the future may look back on the 21st century as the Century of Biology.


A look at precision medicine

Precision medicine is the ability to understand and treat disease at a molecular level and it is driving revolutionary change in fields such as oncology. It aims to improve therapeutic outcomes by adding a previously missing but critical factor – the unique biology of the patient being incorporated into the treatment equation. This is done by including DNA sequence information.

According to the U.S. Food and Drug Administration, “Precision medicine, sometimes known as “personalised medicine” is an innovative approach to tailoring disease prevention and treatment that takes into account differences in people’s genes, environments, and lifestyles. The goal of precision medicine is to target the right treatments to the right patients at the right time.”

Based on this foundation, one megatrend to keep an eye on is cellular manufacturing. This is the ability to reprogram cells for practical purposes and it is transforming industrial biotechnology. Many chemicals and materials traditionally produced through petrochemical processes are now the products of engineered biological cells. Cellular manufacturing also requires a deep understanding of cellular metabolism and pathway interdependencies which are being accelerated by the vast amount of metabolomic information becoming available through advancements in mass spectrometry.

Although mass spectrometry is not new, its application in the clinical realm is fairly recent by medical research standards. For over half a century, diagnostics relied on immunoassays but mass spectrometry is addressing many of the limitations of immunoassays and also becoming vitally important to precision medicine. The high accuracy and sensitivity of mass spectrometric analysis of proteomes are suited for the incorporation of proteomics into precision medicine. Mass spectrometry can provide an understanding of how a patient reacts and interacts with a drug. With new instruments now able to easily fit on a benchtop and deliver results accurately at remarkable speeds with lower costs, it’s become the perfect test for precision medicine patient management.


A key example of megatrend impact: Cardiovascular disease

Inroads are being made in the treatment of cardiovascular disease through sequencing of the PCSK9 gene where it was discovered that various mutations of this gene are associated with high low-density lipoproteins (LDL) cholesterol levels a factor in multiple diseases. The knowledge that this gene plays a role—that high LDL levels weren’t simply a matter of poor diet—has contributed to the development of inclisiran, a small or short interfering RNA (siRNA) therapeutic that acts to silence the PCSK9 gene and effect clinically significant reductions in LDL cholesterol levels. Sequencing and mass spectrometry are essential to identify which patients have mutations in the PCSK9 gene to identify candidates for inclisiran therapy.


The future: Predicting biology

The megatrends of precision medicine and cellular manufacturing share a common driver: the past 20 years have seen a marked shift in our ability to understand and characterise biology as a primarily qualitative science to one that is increasingly quantitative. This shift carries the promise of eventually allowing us to understand, model and predict biology in the same way that we are able to do in the physical sciences—an exceptionally complex proposition that lies beyond our current capabilities. At a fundamental level, as our capacity to understand and control biology at the molecular level deepens our understanding of disease fuels parallel advances in industrial biotechnology.

This article was originally published by Agilent and has been amended here.