Overview
The ASOmatic is a conceptual hardware design that streamlines antisense oligonucleotide (ASO) development against critical disease-implicated proteins, particularly proteins responsible for stress granule formation. Because TDP-43 aggregation, a major hallmark of ALS, depends on stress granule formation, we developed this tool for scientists to generate and test ASO candidates rapidly given the protein they are attempting to knock down. Although not yet fully developed, the model serves as a design that could eventually guide engineers and biologists in creating a real platform for translational research.
The main purpose of the ASOmatic is to automate and standardize the complex steps that are involved in the development of ASOs. Instead of manually sequencing proteins, running predictive software, and evaluating ASO targets, the box is meant to encompass all of these processes into one integrated unit. By doing this, the ASOmatic reduces time required to develop ASO candidates and lowers the chance of experimental or human error, allowing researchers to focus on testing only the most promising ASO candidates in the lab. This ultimately supports the broader therapeutic goal of preventing stress granule formation and stopping TDP-43 from aggregating in ALS through more effective research.
Four-Step Workflow.
The ASOmatic works through four main steps:
1. Protein Input: A researcher inputs the protein of interest into the system, along with its encoding mRNA. This could be the liquid form of a known stress granule-associated protein or any other protein that is suspected of influencing stress granule biology. The input may also be completed digitally through the upload of a protein sequence file (FASTA file) or the manual entry of identifiers.
2. Sequence Analysis: Once the protein and mRNA sequence are entered, ASOmatic sequences it to confirm the protein of interest that is being tested using an integrated database and built-in annotation tools. This ensures that the sequence is accurate while highlighting key mRNA regions of interest for potential ASO targeting.
3. ASO Design Pipeline: The machine then inputs the proteins into our ASO development pipeline (see Model page). This algorithm suggests complementary ASO sequences that can bind to the protein’s mRNA and prevent its expression. This system automatically generates a panel of ASO candidates (rather than just one option). This is intended to give scientists more flexibility in selecting the most effective ASO for wet-lab testing.
4. Efficacy Prediction: Finally, the system evaluates each ASO by using our novel predictive model (see Model page). The output of the ASOmatic is the predicted knockdown efficacy and the overall effectiveness of the ASO given the protein of interest. For example, an ASO might score 85% predicted efficacy which would mean it has a high likelihood of strongly reducing target mRNA. This scoring system would allow candidates to be ranked in a clear and quantitative way before moving to wet-lab validation.
Physical Design
The ASOmatic is designed like a compact tower unit that resembles a high-performance gaming PC. This design allows for modularity, meaning that researchers can easily upgrade components as the technology improves. The main casing is constructed from lightweight aluminum alloy, which is chosen for durability and heat dissipation. The inner shell is reinforced with polycarbonate panels, which provides protection while keeping the unit lightweight. Inside, a liquid cooling system helps maintain stable performance during longer computational tasks, thereby preventing overheating.
System Visuals
Below are visuals of vital system components.
Figure 1. Conceptual model of the ASOmatic hardware, designed in Blender to visualize the system. Click each image to explore more!
Cost & Upgradability
For cost optimization, the system uses commercial-grade processors instead of custom, overly specialized hardware, which helps balance performance with affordability. The modular design also means that individual components (like the sequencing module or prediction engine) can be upgraded without replacing the entire system, which makes it financially sustainable for research labs.
Status & Intended Impact
The ASOmatic has not yet been built; instead, it exists as a conceptual prototype that we plan on developing into a usable tool. Its purpose is to provide scientists with a clear model of how an automated ASO development system could function. By reducing manual trial-and-error processes, the system would help researchers move more quickly from protein identification to therapeutic candidate testing. Ultimately, the ASOmatic represents a layered strategy against ALS which enables for faster ASO discovery and potentially improves the pipeline for future therapy.