gene therapy

Season 4, Episode 2: Powering the Biocomputing Revolution with LatchBio

Episode Contributors: Michael Chavez, Ashton Trotman-Grant, Ayush Noori, Alfredo Andere, Kyle Giffin, Kenny Workman

Episode Summary: Imagine if every graphics design company built its own version of Photoshop in-house. That’s exactly what’s happening today in biology research. Ten-fold increases in data every two years are forcing every biology team to build out their own, in-house bioinformatics stack to store, clean, pipe, and manage the massive volumes of data generated by their experiments. All that work has to happen even before teams can analyze the results! Recognizing this obstacle to high-throughput biology research, Alfredo, Kenny and Kyle built LatchBio to bring the modern computing stack to biotech. By uniting wet lab experiments with dry lab processing, storage, and analyses, LatchBio is democratizing access to top-notch bioinformatics and empowering biologists to derive relevant insights from their data that can move our world forward. Tune in to learn more about their journey from Berkeley dropouts to entrepreneurs building no-code tools to power the biocomputing revolution.

About the Team

  • Alfredo Andere, CEO, was born in Mexico City and raised in Guadalajara, Mexico. He majored in Computer Science and Electrical Engineering and minored in Math at UC Berkeley before dropping out to co-found LatchBio.

  • Kyle Giffin, COO, attended UC Berkeley to study Cognitive Neuroscience and Data Science before dropping out to found LatchBio.

  • Kenny Workman, CTO, started engaging in molecular biology research when he was 15, first at local community colleges as a lab hand and then at MIT and UC Berkeley over successive summers. Prior to co-founding LatchBio, he worked at Asimov and Serotiny as a Software and Machine Learning Engineer.

Key Takeaways

  • After hundreds of interviews with biotech leaders to discover pain points around managing data, the founders developed the LatchAI platform.

  • Common biology analyses require piping gigabytes/terabytes of data, meaning data storage and retrieval require programming expertise.

  • Although scientists may be experts in biological theory and wet lab experimentation, programming expertise is scarce. Biologists must rely on limited computational analysts to process and visualize their data; thus, access to bioinformaticians is a bottleneck in the scientific discovery process.

  • On the flip side, bioinformaticians are often hampered by repetitive analysis tasks, preventing them from innovating new computational methods.

  • Recognizing this disconnect between biologists and bioinformaticians, Alfredo, Kenny, and Kyle launched LatchBio: an end-to-end biocomputing platform to allow both wet lab and dry lab scientists to get back to what they’re trained to do - science!

  • The team recently launched their SDK - a Python native developer toolkit - to bridge the divide between the computationally literate bioinformaticians and the no-code savvy biologists.

  • The goal of LatchBio is to become the universal cloud computing platform for academic research and industry biotech.

Impact

  • The no-code platform that LatchBio is building is bringing the modern computing stack to biotech, streamlining data analysis so scientists can focus on solving the world’s biggest problems with biology.

Company: LatchBio


Season 1, Episode 3: Evolving AAVs for Gene Therapy with Pierce Ogden

First Author: Pierce Ogden

Episode Summary

Powered by synthetic biology, Pierce Ogden makes ALL possible mutations to an adeno-associated virus (AAV) outer shell and rapidly screens them to dissect their attributes. Pierce discusses the technological advances that make this breakthrough screen possible and the novel properties that were discovered. AAVs are rapidly becoming the prefered way to perform gene therapy, correcting cells that carry disease-causing mutations through genetic modification. This technology forms the basis for company Dyno Therapeutics.

About the Author

  • Pierce performed this work as a postdoc at Harvard University in the lab of Professor George Church. Professor Church is one of the founding fathers of synthetic biology and the lab is renowned for developing high throughput methods to design, build, and test bioengineered parts.

  • In his role as Co-Founder & CSO at Manifold Bio, Pierce utilizes his multiplexing expertise to uncover the design principles of protein therapeutics and make new drugs faster than ever before.

Key Takeaways

  • Gene therapy uses genetic information as a drug, correcting cells that carry disease-causing mutations.

  • The inability to deliver these genes to the correct cells limits the widespread adoption of gene therapy.

  • Adeno-associated viruses (AAVs) are an extremely promising way to deliver DNA to human cells. Their outer shell, or capsid, can be engineered for increased safety, specificity, and shelf-life.

  • Using advances in DNA synthesis technology, all possible single mutations to the AAV capsid are generated.

  • With a DNA barcode read through next generation sequencing, this AAV library was simultaneously tested cheaply and quickly to find mutations with improved properties.

  • Increased thermal stability, evasion of immune responses, and specificity toward the brain were all found. 

Translation

  • Pierce demonstrates that smart usage of our synthetic biology toolbox can allow millions of protein variants to be tested simultaneously, in direct opposition to the “tested in parallel” model that has dominated high-throughput biology.

  • Manifold Bio takes this idea of DNA barcodes coupled with simultaneous screening and points it toward the field of protein therapeutics.

Paper: Comprehensive AAV capsid fitness landscape reveals a viral gene and enables machine-guided design. Science, 2020