RNAGenScape: Property-Guided, Optimized Generation of mRNA Sequences with Manifold Langevin Dynamics

TL;DR

RNAGenScape is a novel property-guided manifold Langevin dynamics framework that generates biologically viable, property-optimized mRNA sequences by operating on a learned data manifold, improving sequence quality and success rates.

Contribution

It introduces a new manifold-based optimization method for mRNA sequence generation that maintains biological viability and enhances property optimization over existing methods.

Findings

Increases median property gain by up to 148%.

Improves success rate by up to 30%.

Ensures biological viability of generated sequences.

Abstract

Generating property-optimized mRNA sequences is central to applications such as vaccine design and protein replacement therapy, but remains challenging due to limited data, complex sequence-function relationships, and the narrow space of biologically viable sequences. Generative methods that drift away from the data manifold can yield sequences that fail to fold, translate poorly, or are otherwise nonfunctional. We present RNAGenScape, a property-guided manifold Langevin dynamics framework for mRNA sequence generation that operates directly on a learned manifold of real data. By performing iterative local optimization constrained to this manifold, RNAGenScape preserves biological viability, accesses reliable guidance, and avoids excursions into nonfunctional regions of the ambient sequence space. The framework integrates three components: (1) an autoencoder jointly trained with a property predictor to learn a property-organized latent manifold, (2) a denoising autoencoder that projects updates back onto the manifold, and (3) a property-guided Langevin dynamics procedure that performs optimization along the manifold. Across three real-world mRNA datasets spanning two orders of magnitude in size, RNAGenScape increases median property gain by up to 148% and success rate by up to 30% while ensuring biological viability of generated sequences, and achieves competitive inference efficiency relative to existing generative approaches.