Denovo PiggyBac transposon generation

Apply genomic language models (e.g., evo2) for denovo PiggyBac transposon generation.

Overview

We are designing de novo PiggyBac (PB) transposons using generative sequence models, pursuing two complementary strategies.

  1. We focus on the transposase protein itself, fine-tuning protein language models (e.g., ProGen2, ProtGPT3) on a large in-house PiggyBac dataset via SFT, then using reinforcement learning to align generated sequences with experimentally measured high-activity variants.

  2. We design the entire PB element from scratch using genomic language models (e.g., Evo2), fine-tuned on in-house PB data to generate complete transposon sequences de novo.

Designs from both approaches are currently being validated experimentally in the lab.