The science of delivering cures straight to your cells | Eric Kelsic

Quick Overview

Eric Kelsic, CEO and co-founder of Dyno Therapeutics, discusses how they leverage directed evolution and AI to engineer Adeno-Associated Virus (AAV) capsids, the protein shells used as delivery vehicles in gene therapy, with the goal of significantly reducing the cost and increasing the efficiency and safety of these potentially curative treatments for rare genetic diseases.

Key Points: Eric Kelsic, CEO and co-founder of Dyno Therapeutics, has been working for 10 years to solve the grand challenge of gene therapy delivery. The core technology involves engineering AAV capsids, which naturally evolved to infect cells, to direct therapeutic payloads to specific cell types, such as neurons in the brain, which is otherwise hard to reach. Dyno uses Directed Evolution, similar to the process that drove cost reductions in solar PV (Wright's Law), to rapidly test millions of capsid sequences to find optimal variants. The company has generated 1 PB of DNA sequencing data from experiments testing millions of capsid variants, using AI models to analyze this data and guide the next round of evolution. Gene therapies like Zolgensma (for SMA) are extremely expensive, costing millions, and the goal of Dyno's technology is to reduce this cost to make treatments more accessible. The process involves high-throughput screening of engineered capsids to find variants that are more effective and safer for specific organs or cell types.

Context: Eric Kelsic is the CEO and co-founder of Dyno Therapeutics, a company focused on advancing gene therapy by engineering better delivery vehicles using their proprietary technology. The video frames the discussion around the immense challenge of delivering therapeutic genetic material precisely to the correct cells within the human body, contrasting the high costs and limitations of current treatments with the potential of AI-driven directed evolution.

Detailed Analysis

Eric Kelsic, CEO and co-founder of Dyno Therapeutics, explains that the fundamental challenge in gene therapy is delivery—getting the therapeutic DNA payload into the correct cells for a lifetime of function. He highlights that while many genetic diseases are known (like SMA, which was fatal in infants before treatments like Zolgensma), current AAV delivery systems are not efficient or targeted enough for systemic treatment, often only reaching a small fraction of target cells (e.g., 0.1% of neurons in the brain). Dyno Therapeutics addresses this by applying Directed Evolution, similar to Wright's Law observed in the drastic cost reduction of solar PV over decades. They engineer the AAV capsid—the virus's protein shell—to optimize its targeting capabilities. This involves generating vast libraries of capsid sequences (1 PB of data mentioned) and using AI models to analyze the resulting functional data to iteratively design better variants. Kelsic notes that while existing FDA-approved AAV therapies like Zolgensma cost millions and target specific diseases, the goal is to create highly efficient delivery vehicles that can be customized for any tissue or organ, ultimately driving down the cost and broadening the applicability of gene therapy.