Title : Democratizing ASO drug discovery at La Jolla Labs
Abstract:
La Jolla Labs is a startup biotechnology company based in San Diego County, California, USA that values patient safety first. La Jolla Labs works to leverage RNA biology, automation, cloud computing and machine learning to deliver transformative medicine to patients with rare diseases. La Jolla Labs specializes in computational biology through software creation and antisense oligonucleotide (ASO) technology. Housed within our proprietary ASO design software, we built a “LJ Splice” machine learning-based, computational model. This model leverages cis sequence features that are predictive of important exon inclusion or exon exclusion events at splice acceptor and splice donor sites. This carefully designed model can be leveraged to guide steric blocking ASO design strategies with the goal of influencing alternative splicing or other RNA-regulatory events. We demonstrate the predictive power of LJ Splice to inform rationale steric blocking ASO design to minimize costs and maximize efficacy. This highly efficient design process is then paired with our streamlined, high throughput in vitro screening laboratory to screen designed ASO candidates. We focus this screening at the RNA level, where ASOs function. We have employed this technology to both upregulate and downregulate targets, modulate splicing changes and achieve allele-specific knockdown. The combined effect of our ASO design software and in house screening laboratory permits initial ASO lead compound identification at a fraction of the cost of traditional design approaches. We believe further model refinement and in vitro data validation will allow many more rare disease groups to access the initial stages of ASO drug development, thus helping to democratize ASO drug discovery.
