# Multimodal Alignment and Preference Optimization for Zero-Shot Conditional RNA Generation

arXiv: https://arxiv.org/abs/2605.23961 · HTML: https://mlsanity.com/paper/2605.23961/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Preference optimization for molecular design, one of 10 directions in LLM alignment / RLHF / preference optimisation.
- Builds on 28 of its 84 references that are in the map.
- First posted on arXiv 12 May 2026.

## Placed in

- LLM alignment / RLHF / preference optimisation / [Preference optimization for molecular design](https://mlsanity.com/alignment/preference-optimization-for-molecular-design/)

## Builds on (most cited first, 28 of 28)

- [Learning Transferable Visual Models From Natural Language Supervision](https://mlsanity.com/paper/2103.00020/) (2021)
- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [Training language models to follow instructions with human feedback](https://mlsanity.com/paper/2203.02155/) (2022)
- [Exploring the Limits of Transfer Learning with a Unified Text-to-Text Transformer](https://mlsanity.com/paper/1910.10683/) (2019)
- [LoRA: Low-Rank Adaptation of Large Language Models](https://mlsanity.com/paper/2106.09685/) (2021)
- [Chain-of-Thought Prompting Elicits Reasoning in Large Language Models](https://mlsanity.com/paper/2201.11903/) (2022)
- [Direct Preference Optimization: Your Language Model is Secretly a Reward Model](https://mlsanity.com/paper/2305.18290/) (2023)
- [BLIP-2: Bootstrapping Language-Image Pre-training with Frozen Image Encoders and Large Language Models](https://mlsanity.com/paper/2301.12597/) (2023)
- [RoFormer: Enhanced Transformer with Rotary Position Embedding](https://mlsanity.com/paper/2104.09864/) (2021)
- [Flamingo: a Visual Language Model for Few-Shot Learning](https://mlsanity.com/paper/2204.14198/) (2022)
- [Finetuned Language Models Are Zero-Shot Learners](https://mlsanity.com/paper/2109.01652/) (2021)
- [Training a Helpful and Harmless Assistant with Reinforcement Learning from Human Feedback](https://mlsanity.com/paper/2204.05862/) (2022)
- [Gaussian Error Linear Units (GELUs)](https://mlsanity.com/paper/1606.08415/) (2016)
- [Scaling Instruction-Finetuned Language Models](https://mlsanity.com/paper/2210.11416/) (2022)
- [The Curious Case of Neural Text Degeneration](https://mlsanity.com/paper/1904.09751/) (2019)
- [Fine-Tuning Language Models from Human Preferences](https://mlsanity.com/paper/1909.08593/) (2019)
- [Shortcut Learning in Deep Neural Networks](https://mlsanity.com/paper/2004.07780/) (2020)
- [LIMA: Less Is More for Alignment](https://mlsanity.com/paper/2305.11206/) (2023)
- [On the Convergence of Adam and Beyond](https://mlsanity.com/paper/1904.09237/) (2019)
- [Scaling Vision Transformers to 22 Billion Parameters](https://mlsanity.com/paper/2302.05442/) (2023)
- [Faith and Fate: Limits of Transformers on Compositionality](https://mlsanity.com/paper/2305.18654/) (2023)
- [Scaling Data-Constrained Language Models](https://mlsanity.com/paper/2305.16264/) (2023)
- [LoRA Learns Less and Forgets Less](https://mlsanity.com/paper/2405.09673/) (2024)
- [Smaug: Fixing Failure Modes of Preference Optimisation with DPO-Positive](https://mlsanity.com/paper/2402.13228/) (2024)
- [Unintentional Unalignment: Likelihood Displacement in Direct Preference Optimization](https://mlsanity.com/paper/2410.08847/) (2024)
- [RNAFlow: RNA Structure & Sequence Design via Inverse Folding-Based Flow Matching](https://mlsanity.com/paper/2405.18768/) (2024)
- [Diversity in Large Language Models under Supervised Fine-Tuning](https://mlsanity.com/paper/2605.00195/) (2026)
- [BAnG: Bidirectional Anchored Generation for Conditional RNA Design](https://mlsanity.com/paper/2502.21274/) (2025)

## Abstract (arXiv)

The design of RNA molecules that interact with specific proteins is a critical challenge in experimental and computational biology. Despite recent progress in natural language modeling and deep learning-based protein design, there remains significant room to improve the frequency of successful interactions and the authenticity of generated sequences for functional applications. In this work, we frame conditional RNA sequence generation as a multi-stage alignment problem, introducing Moirain: a suite of models optimized via multimodal supervised fine-tuning (SFT) and Direct Preference Optimization (DPO). Our approach begins with large-scale pretraining on diverse RNA corpora to capture the fundamental grammars of sequence plausibility. To achieve target-specific generation, we employ a multimodal SFT architecture that conditions RNA synthesis on protein structural and sequential features. Finally, we leverage DPO to refine the model using synthetic interaction data: taking advantage of DPO's unique ability to navigate non-aligned preference spaces, we improve functional fitness without collapsing the learned natural distribution. Extensive evaluation of the Moirain series (Moirain-Base, -Multi, and -DPO) demonstrates that our framework consistently produces novel, diverse, and biologically plausible RNA sequences with superior binding affinities compared to existing baselines.