Modern medicine is closely tied to the scientific advances of the last hundred or so years. The speed of that progress can be hard to put into scope, but it was only in 1928 that Alexander Fleming discovered penicillin, revolutionizing the world of Drug Discovery with the first widely applicable antibiotic.
Like many incredible scientific achievements, Fleming found the new treatment by accident. What would become known as penicillin was simply growing as a mold in an uncovered Petri dish. His team spent years researching the discovery and it wasn’t until 1945 that they received the Nobel Prize in medicine.
As time went on biomedical research and Drug Discovery have only become more sophisticated. The pharmaceutical industry is constantly driven to better understand diseases and develop treatments more efficiently. In the modern era, gene silencing and reverse genetics are at the forefront of almost every new discovery in medicine, and CRISPR Cas 9 and Zebrafish are leading the charge.
In this article, we'll explain what CRISPR is and how it can be used with Zebrafish research.
What is CRISPR?
Seen as something like the penicillin of gene editing, CRISPR has been a powerful driving force behind that shift in focusing on individual genes. None of that would have been possible without Francisco Martínez Mojica putting together the initial pieces of the puzzle in the early 90s.
His work involving Haloferax and Haloarcula led to the discovery of a new set of features that were tied to an adaptive immune system. Mojica would go on to name the new system Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR for short.
When the scientific community noticed how CRISPR could be used for precise and efficient gene editing, a revolution began.
Genome editing in some form has been possible since the 1980s, but it was always rather difficult to use and almost impossible to apply at a large scale. CRISPR simplified everything, giving scientists a pair of gene cutting scissors to make their own edits to DNA sequences. Following RNA guide strands, CRISPR acts as a tool that can cut genes at very specific locations.
With Mojica’s work and what eventually became CRISPR, researchers have an incredible level of control over the Drug Discovery process. Editing individual genes with unmatched precision transforms scientists into artists and architects as they observe the exact effects of new treatments and new diseases.
CRISPR Cas9 and Zebrafish
Gene editing and reverse genetics have simplified over time with the discovery of tools like CRISPR and morpholinos. While that has translated into faster and more reliable research, it has also created a larger demand for relevant animal models.
Choosing the right animal model is always dependent on the goals of the research and the combination of genes, diseases, and treatments. However, all Drug Discovery has a need for reliable models that allow for large scale testing of toxicity, efficacy, and safety. Research into how genes manifest themselves requires the use of reliable animal models.
In early Drug Discovery and preclinical studies, Zebrafish research offers clear advantages over other alternative animal models. The complete genome sequence is already available and 85% of human disease genetic DNA has an orthologue in Zebrafish. Being vertebrates that produce many offspring in quick reproduction cycles, the small fish are often the perfect candidate for any tests and assays in early Drug Discovery and preclinical studies.
It may seem unusual for Zebrafish to have such a complete genome sequence, but it comes down to the fish already having a proven history as a reliable animal model. The oligomer molecules that are morpholinos have been used in Zebrafish to explore the interactions between specific DNA sequences and gene expression for decades.
Zebrafish provide scientists and researchers with an animal model that ensures results are reliable, verifiable, and applicable to humans.
With a proven track record in reverse genetics, using CRISPR Cas9 and Zebrafish was an easy extension of the well documented animal model. As another solid example to prove that point, Zebrafish were the first vertebrates used to demonstrate the possibility of in vivo gene editing with CRISPR.
CRISPR with Zebrafish Allows for New Discoveries in Medicine
When Francisco Martínez Mojica was first looking into archaeal organisms, he couldn’t imagine the impact it would have on Drug Discovery and the advancements it would allow for in medicine. Like Alexander Fleming before him, Mojica emphasizes that these impactful discoveries only happen when science is seen as an active pursuit of new knowledge.
The elegance of CRISPR is how it combines precision, ease-of-use, and scalability. To put it mildly, Mojica’s discovery fundamentally changed the way scientists and researchers look at Drug Discovery. New treatments for new diseases now rely on that ability to edit individual genes and DNA sequences, something that granted the Nobel Prize to both Emmanuelle Charpentier and Jennifer Doudna.
Gaining access to a tool that is easy to use and scale means the entire process can move faster while also ensuring all results are verifiable. In other words, CRISPR allows scientists and researchers to more reliably look into potential new treatments.
Having a readily available vertebrate animal model to test promising molecules and chemical compounds is an important part of Drug Discovery. With CRISPR Cas9 and Zebrafish, scientists can look into how an abstract trait will eventually appear in the full biological system.
Through the use of CRISPR Cas9 and Zebrafish, pharmaceutical companies are not only staying on the cutting edge of scientific knowledge, they are also staying ahead of any changes in the biomedical industry.
The ability to perform the right tests and assays as early as possible directly translates into more promising leads and eventually bringing new treatments, drugs, and vaccines to the world.