Artan Bio Background
Artan Bio made its debut late last year when the VitaDAO community used Molecule’s IP-NFT framework to fund $91,000 USD worth of work for developing and testing tRNA suppressors in cells with specific mutations. This funding led to the creation of in vitro assays and the development of 15 potential drug candidates.
Since then, the VitaDAO community has further supported Artan Bio through a successful crowdsale of IP Tokens, raising an additional $300,000 USD in 10 days. The goal of these funds was to find and further develop lead drug candidate(s) via in vitro assays, package candidates into a drug delivery modality, and then move them into animal models to assess efficacy. Of the 15 drug candidates that were developed, at least 2 showed some promise in correcting nonsense mutations in the cell line used in the experiments.
Let’s explore their approach and review the findings in detail.
What Is a DNA Mutation?
To start, let’s give some background on DNA mutations. DNA mutations are changes or "mistakes" in our DNA, the molecule that carries the instructions for building and maintaining our bodies. Think of DNA as a recipe book that contains all the information needed to create proteins, the building blocks that make up our cells. A mutation is like a typo in this recipe book—sometimes it’s harmless, but other times it can cause serious problems by producing a faulty protein or no protein at all.
Types of DNA Mutations
There are several types of DNA mutations. Some of the most common include:
- Silent Mutations: These mutations do not change the final protein produced, so they often go unnoticed.
- Missense Mutations: These mutations change one of the "letters" in the DNA, which can result in a different protein being made.
- Nonsense Mutations: Nonsense mutations create a premature “stop” signal (codon) in the DNA. Imagine reading a sentence, and suddenly there is a period in the middle of a word. The result is an incomplete protein that doesn’t work correctly or at all. These mutations are the focus of Artan Bio.
Nonsense Mutations and Codons
To understand nonsense mutations better, we need to know about codons. Codons are like words in the DNA language. Each codon consists of three DNA "letters" (nucleotides) that tell the cell which amino acid (building block of protein) to add next.
One important codon is CGA, which instructs the cell to add the amino acid arginine. Nonsense arginine mutations are common in proteins related to DNA damage, neurodegeneration, and tumor suppression. The Artan BIO team is specifically focused on restoring protein levels and function for arginine nonsense mutations to treat age-related diseases.
Targeting Mutations for Treatment: Viruses to the Rescue
Researchers at Artan Bio are focused on finding ways to correct these CGA nonsense mutations to restore healthy protein levels. To correct these mutations, the researchers are using a gene therapy approach, which involves delivering a healthy copy of the gene directly into cells to replace or repair the faulty one. Artan Bio is using what’s called a “suppressor tRNA” system which is able to recognize the mutation in DNA letters, and inserts the correct letter in its place. To do this, we can use the skills of an old enemy-turned-friend: adenoviruses.
What Are Adenoviruses and Why Are They Used in Treatments?
Imagine you need to deliver a very important package to a specific address. You could try many different delivery methods, but you’d probably choose the most reliable one that reaches the most places. In medicine, when scientists need to deliver a new gene or treatment directly into cells, they can use a “delivery vehicle” called a vector—and that’s where adenoviruses like AAV9 come in.
Adenoviruses are a type of virus that usually cause mild illnesses, like the common cold. However, scientists have found a way to turn them into helpful tools for delivering treatments. AAV9 (Adeno-Associated Virus 9) is a special type of adenovirus that is FDA approved, and has been modified in the lab to remove its ability to cause disease. So, while AAV9 is technically still a virus, it’s like a harmless delivery truck that can carry helpful genetic instructions into the cells.
How Is Artan BIO Using AAV9 Vectors in Their Treatment?
In gene therapy, scientists use AAV9 to deliver healthy copies of a gene into cells to replace or fix faulty genes that cause diseases. In the case of Artan Bio, the virus is used to carry and deliver their engineered suppressor system that specifically recognizes nonsense mutations in CGA codon to restore normal protein levels and function.
Tools to measure that a treatment is working
To make sure their gene therapy approach is effective, Artan Bio is using several tests to measure the important variables.
One key test is a Western blot, which allows scientists to answer questions like
- Is a certain protein present in a sample (yes/no)
- At what level is that protein expressed, and how does it compare to a healthy vs diseased state (how much)
In the current data, p53 (a key protein involved in tumor suppression), is measured in a cell line that carries the arginine nonsense mutation of interest (Calu-6 cells). The cells naturally carry this mutation, so if you leave them to grow on their own, they will not produce the full p53 protein since the mutation is blocking this process. However, if you add a virus carrying Artan Bio’s suppressor system to the cells, it looks like some of the tested conditions were able to “suppress” the mutation and restore the cells’ natural ability to produce the protein - a successful initial result! Let’s take a look at the results more deeply to understand how the researchers were able to draw these conclusions.
Artan Bio In Vitro Results
Results 1: Restoring Production of p53 Protein
In their tests, Artan Bio designed several vectors to rescue an arginine nonsense mutation in p53 in the Calu-6 cell line. Of the 5 vectors tested, 2 showed positive results for rescuing p53 protein levels (lanes 4 and 5 in the image above; labels Vec2 and Vec3). These results are from a technique called a “Western blot”, and the darkness of the band is indicative of how much protein is present (darker band = more protein). These results show that the suppression vectors that have been created by Artan Bio are able to increase p53 protein production in the tested cell line.
The important thing to note here is that these vectors can be effective if they are able to get into the cell. This is easy to test and control for in cells tested in the lab, but the methods here cannot be used to treat people. In order for the vector to reach where it needs to go in humans, it needs to be packaged into its delivery vehicle. This is where the AAV9 virus comes back in. Therefore, the next thing to test for was the ability of the AAV9 virus to enter the same cell line, showing that (1) it would be capable of delivering the vector cargo and (2) the vector cargo could then go on to increase p53 protein production.
Results 2: Confirmation that AAV9 carrying vector cargo can enter Calu-6 cells and increase p53 protein production
As always, optimization steps are needed before the “real” experiment can start. As mentioned, the team needed to see what concentration of virus would be required to get the cargo into the cell. Too little, and not enough cargo will be delivered. Too much, and the virus will cause too much toxicity and kill the cells. This relationship is referred to as the multiplicity of infection, or MOI, which is the ratio of infectious agents (AAV9 virus here) to infection targets (the target cell, here Calu-6 cells).
In this first experiment, two conditions were tested (Artan-101 and Artan-102). Cells had virus added to them at two different concentrations to assess which combination of virus concentration and vector would be the most effective at restoring levels of p53 protein. Positive results were obtained in lanes 4 and 6 in the image above, with the most effective condition being seen in lane 6, with a very strong band visible for p53.
Conclusion: The suppressor system (vector), when packaged into the virus, can enter cells and effectively overcome the nonsense mutation to restore the production of the p53 protein in the tested cell line.
What’s Next for Artan Bio’s Research?
With these promising results, the next steps involve scaling up the production Artan-102, the lead candidate, and more extensive studies in animals. Artan Bio will submit a proposal to VITARNA tokenholders to support the feasibility study. This will produce high-quality material sufficient for safety and efficacy studies; critical experiments are needed before testing in humans is possible. If all goes well, this innovative approach could one day help treat or even cure diseases caused by DNA mutations, such as neurodegeneration and cancer.
What Artan Bio Means for DeSci?
While still in its early stages, Artan Bio embodies more than just research advancements— it is proof that decentralized communities can come together to quickly fund and advance innovative research that otherwise would have laid dormant. By using new technologies to democratize funding and create new incentive mechanisms, Artan Bio has not only advanced our scientific understanding of mutations in aging but has moved us one step closer to the transparent and inclusive vision of decentralized science.
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