Powered by genomic sequencing, precision medicine has had some notable success in recent years. A range of genomics-based tests is now available to providers to help them better diagnose disease and improve patient outcomes. For example, women can get tested for BRCA gene mutations to assess their risk of developing breast and ovarian cancer and use the results to make health decisions.
However, progress toward full clinical use of sequencing-based testing has been painstakingly slow. While scientists have uncovered genetic alterations that underpin cancer, neurologic conditions, autoimmune diseases, and more, many of these findings are not yet used to make treatment decisions.
One early contributing factor to the slow progress of precision medicine was the lack of comprehensive diagnostic tests. For many years, genetic tests assessed mutations one gene at a time—a costly, time-consuming, and error-prone process.
This was particularly onerous for children with rare and undiagnosed genetic diseases (RUGDs). Researchers estimate that about 39 percent of RUGD cases have a suspected genetic origin and about half never receive a diagnosis.
In the past, clinicians would make their best guess regarding which gene(s) might be linked to a condition, then conduct iterative tests to confirm their hypothesis. If the first test result was negative, they would test for the next gene on the list. Because it took weeks to get the results from each test, patients and their families often endured frustrating, years-long diagnostic odysseys.
The tools of precision medicine
Clinical next-generation sequencing (NGS) has eliminated some of the guesswork for people with rare conditions. Whole-genome or whole-exome sequencing can provide comprehensive readouts that highlight known clinically relevant mutations.
For example, commercial comprehensive genomic profiling panels can identify multiple driver mutations and assess microsatellite instability in rare cancers. Clinicians can use this data to delineate a patient’s cancer and provide personalized care including targeted treatment options.
In addition to NGS, there are ongoing efforts to use gene editing—specifically CRISPR—to tailor treatments. For example, a team of scientists reported that CRISPR showed promise in clinical trials for effectively changing patients’ immune cells to flag and tackle their tumor cells.
Reprogramming genes and proteins
Another exciting field that has the potential to impact precision medicine is synthetic biology. The technology enables scientists to write high-quality, inexpensive synthetic oligonucleotides—single strands of DNA that are the building blocks for PCR-based diagnostics, as well as vaccines and therapies. Some companies are leveraging synthetic DNA to develop precision biotherapeutics.
Enzymatic DNA synthesis (EDS), a method of manufacturing custom DNA sequences, leverages some of the same processes used in nature. Rather than relying on third-party oligo service providers, labs can purchase their own benchtop DNA-writing instruments, putting them in control of the DNA design process and synthesis workflow from start to finish.
This kind of access is valuable for scientists that test ideas quickly and often. For example, scientists in mobile labs around the world could use EDS to rapidly develop diagnostic tests and therapies for emerging pathogens. Speed is also essential in the context of personalized immunotherapies, where samples from patients’ tumors are used to develop individualized vaccines and therapies.
The future is bright
Diagnostics and therapies developed using methods such as CRISPR or EDS will not become widely available overnight. Though science is evolving rapidly, there remain significant knowledge gaps.
For example, securing approval for novel tests and therapies to enter routine clinical use requires evidence of both improved quality of life and cost-effectiveness. That data is difficult to come by due to patient population sizes—previous studies may be too small to make broad assumptions about a technology’s efficacy. For example, the CRISPR-based gene editing clinical trial only had 16 patients and focused on a subset of solid tumors.
It may be too soon to predict the full impact of sequencing and gene-editing tools, but these early successes bode well for the future of precision medicine.