Who’s Top Dog in the Central Dogma?
As many of you know, Geneoscopy uses RNA biomarkers in stool to develop diagnostic tests to prevent, detect and treat gastrointestinal disease. RNA is essential to our platform, but many of our competitors in the field use DNA. So why have we chosen a different path?
In this article, we will touch on the following questions: What is the difference between DNA and RNA? Why is RNA a better diagnostic tool than DNA? If RNA really is better, why aren’t other companies using it?
What is DNA? DNA contains the genetic code that determines cellular and bodily functions. DNA is composed of four different types of nucleotides, which are rearranged to form different genes. Each cell in your body houses two copies of DNA and has the exact same genetic code. DNA is double stranded which helps protect it from degradation and damage.
What is RNA? RNA is similar to DNA in that it is composed of four different types of nucleotides. However, RNA is single stranded and is made by transcribing unwound DNA. RNA cannot be made without DNA!
Its principal role is to act as a messenger carrying instructions from DNA. The specific types and quantities of RNA in each cell are dependent on the specific requirements of the cell at that point in time. For example, when you eat a lot of food at Thanksgiving dinner, your cells will make more copies of insulin-producing RNA and will accordingly produce more insulin to help regulate blood sugar level.
DNA and RNA Function: Every cell in the body contains two reference copies of the DNA molecule. DNA is a cookbook that holds all the cell’s recipes so that it can grow and divide. RNA is a small copy of the DNA template that cells use to operate. Think of RNA as the recipes that are listed in the DNA cookbook. When a gene is activated at the DNA level, more RNA molecules (transcripts) are produced; conversely, when a gene is inactivated, fewer RNA transcripts are produced. The cell turns RNA recipes on or off based on its interactions with its environment (after all, some recipes are only used for Thanksgiving dinner). RNA allows for the ordering of amino acids to create proteins and enzymes, which are the worker bees of the cell. These amino acids must be added in the correct order and proportion to ensure the turkey comes out just right.
DNA and RNA in Cancer: The cookbook is reliably printed (maybe with a few annotations from Grandma) and replicated with very high reliability. However, sometimes changes do occur (mutations). These changes can be caused by carcinogens, such as cigarette smoke, environmental factors such as UV light exposure, or can be completely random. Too many small changes, or one large change (a tsp becoming a tbsp), can lead to cancer.
Cancer cells are constantly growing and dividing, in contrast to normal cells which grow and divide only at specific times. To facilitate the constant growth and division of cancer cells, RNA levels for genes that promote growth and division are much higher than in normal cells. Cancer cells also produce proteins that create pathways into other parts of the body and there will be higher amounts of RNA for these proteins as well.
Why is RNA better for monitoring disease? DNA consists of 2.4 billion base pairs and there are many DNA mutations that can cause cancer; however, all cancer-causing mutations induce similar downstream RNA changes that can be routinely detected. To continue our analogy, we might say that Aunt Sallie’s legendary rolls are a staple of Thanksgiving dinner, but she brings those rolls at other times of the year besides Thanksgiving. But if after dinner you are tired, your belt is loosened one notch, you have a cranberry stain on your shirt, and cornbread crumbs on your lap, well you can be pretty sure what day it is…. Similarly, the symptoms (RNA) of cancerous cells can be reliably measured to diagnose disease.
Where is the RNA in stool? Enterocytes are cells that line the gastrointestinal (GI) tract. Enterocytes are constantly being shed into the lumen of the GI tract and are excreted in small numbers with food waste and bacterial cells in stool. These enterocytes contain informative RNA that provide a snapshot of GI health.
Why is RNA hard to measure in stool? Unlike DNA, which is exceptionally durable, RNA is very temperamental. It is readily degraded in stool samples. What’s more, enterocytes found in stool samples are in the midst of apoptosis, meaning that these cells are undergoing programmed cell death. Cell death results in heavy degradation of the RNA biomarkers. The majority of cells in stool samples are also bacterial, which creates a problem with background signal (i.e. noise). It is harder to get a reliable human RNA signal from stool samples, so while researchers have been relatively successful in isolating human DNA, accurate measurements of RNA have been elusive.
What has Geneoscopy done about this? Geneoscopy has developed a method to effectively isolate informative RNA biomarkers from stool samples. RNA analysis provides a snapshot of real-time cellular conditions with increased sensitivity compared to DNA analysis. This allows us to create noninvasive diagnostic tools to improve GI health that provide a level of information and insight beyond that of a DNA-based test. We are currently developing a preventive screening test for colorectal cancer and several other products for GI-related conditions. But for more information on our pipeline, you will have to wait for a future newsletter…
