Helix-mRNA: A Hybrid Foundation Model For Full Sequence mRNA Therapeutics

Fuente: arXiv
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Main Authors: Wood, Matthew, Klop, Mathieu, Allard, Maxime
Format: Preprint
Published: 2025
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author Wood, Matthew
Klop, Mathieu
Allard, Maxime
author_facet Wood, Matthew
Klop, Mathieu
Allard, Maxime
contents mRNA-based vaccines have become a major focus in the pharmaceutical industry. The coding sequence as well as the Untranslated Regions (UTRs) of an mRNA can strongly influence translation efficiency, stability, degradation, and other factors that collectively determine a vaccine's effectiveness. However, optimizing mRNA sequences for those properties remains a complex challenge. Existing deep learning models often focus solely on coding region optimization, overlooking the UTRs. We present Helix-mRNA, a structured state-space-based and attention hybrid model to address these challenges. In addition to a first pre-training, a second pre-training stage allows us to specialise the model with high-quality data. We employ single nucleotide tokenization of mRNA sequences with codon separation, ensuring prior biological and structural information from the original mRNA sequence is not lost. Our model, Helix-mRNA, outperforms existing methods in analysing both UTRs and coding region properties. It can process sequences 6x longer than current approaches while using only 10% of the parameters of existing foundation models. Its predictive capabilities extend to all mRNA regions. We open-source the model (https://github.com/helicalAI/helical) and model weights (https://huggingface.co/helical-ai/helix-mRNA).
format Preprint
id arxiv_https___arxiv_org_abs_2502_13785
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Helix-mRNA: A Hybrid Foundation Model For Full Sequence mRNA Therapeutics
Wood, Matthew
Klop, Mathieu
Allard, Maxime
Genomics
Artificial Intelligence
mRNA-based vaccines have become a major focus in the pharmaceutical industry. The coding sequence as well as the Untranslated Regions (UTRs) of an mRNA can strongly influence translation efficiency, stability, degradation, and other factors that collectively determine a vaccine's effectiveness. However, optimizing mRNA sequences for those properties remains a complex challenge. Existing deep learning models often focus solely on coding region optimization, overlooking the UTRs. We present Helix-mRNA, a structured state-space-based and attention hybrid model to address these challenges. In addition to a first pre-training, a second pre-training stage allows us to specialise the model with high-quality data. We employ single nucleotide tokenization of mRNA sequences with codon separation, ensuring prior biological and structural information from the original mRNA sequence is not lost. Our model, Helix-mRNA, outperforms existing methods in analysing both UTRs and coding region properties. It can process sequences 6x longer than current approaches while using only 10% of the parameters of existing foundation models. Its predictive capabilities extend to all mRNA regions. We open-source the model (https://github.com/helicalAI/helical) and model weights (https://huggingface.co/helical-ai/helix-mRNA).
title Helix-mRNA: A Hybrid Foundation Model For Full Sequence mRNA Therapeutics
topic Genomics
Artificial Intelligence
url https://arxiv.org/abs/2502.13785