# AAVGen: Precision Engineering of Adeno-associated Viral Capsids for Renal Selective Targeting

arXiv: https://arxiv.org/abs/2602.18915 · HTML: https://mlsanity.com/paper/2602.18915/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 3 of its 33 references that are in the map.
- First posted on arXiv 21 Feb 2026.

## Builds on (most cited first, 3 of 3)

- [Training language models to follow instructions with human feedback](https://mlsanity.com/paper/2203.02155/) (2022)
- [Group Sequence Policy Optimization](https://mlsanity.com/paper/2507.18071/) (2025)
- [AAVDiff: Experimental Validation of Enhanced Viability and Diversity in Recombinant Adeno-Associated Virus (AAV) Capsids through Diffusion Generation](https://mlsanity.com/paper/2404.10573/) (2024)

## Built on by (most cited first, 1 of 1)

- [Apodex Discovery: Reality Benchmarks and Environments for Evaluating and Building Discoverative Artificial Intelligence](https://mlsanity.com/paper/2608.11341/) (2026)

## Abstract (arXiv)

Adeno-associated viruses (AAVs) are promising vectors for gene therapy, but their native serotypes face limitations in tissue tropism, immune evasion, and production efficiency. Engineering capsids to overcome these hurdles is challenging due to the vast sequence space and the difficulty of simultaneously optimizing multiple functional properties. The complexity also adds when it comes to the kidney, which presents unique anatomical barriers and cellular targets that require precise and efficient vector engineering. Here, we present AAVGen, a generative artificial intelligence framework for de novo design of AAV capsids with enhanced multi-trait profiles. AAVGen integrates a protein language model (PLM) with supervised fine-tuning (SFT) and a reinforcement learning technique termed Group Sequence Policy Optimization (GSPO). The model is guided by a composite reward signal derived from three ESM-2-based regression predictors, each trained to predict a key property: production fitness, kidney tropism, and thermostability. Our results demonstrate that AAVGen produces a diverse library of novel VP1 protein sequences. In silico validations revealed that the majority of the generated variants have superior performance across all three employed indices, indicating successful multi-objective optimization. Furthermore, structural analysis via AlphaFold3 confirms that the generated sequences preserve the canonical capsid folding despite sequence diversification. AAVGen establishes a foundation for data-driven viral vector engineering, accelerating the development of next-generation AAV vectors with tailored functional characteristics.