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Designing messenger RNA (mRNA) sequences for a fixed target protein requires searching an exponentially large synonymous space while optimizing properties that affect stability and downstream performance. This is challenging because…

Biomolecules · Quantitative Biology 2026-03-09 Feipeng Yue , Ning Dai , Wei Yu Tang , Tianshuo Zhou , David H. Mathews , Liang Huang

The task of RNA design given a target structure aims to find a sequence that can fold into that structure. It is a computationally hard problem where some version(s) have been proven to be NP-hard. As a result, heuristic methods such as…

Biomolecules · Quantitative Biology 2024-12-13 Wei Yu Tang , Ning Dai , Tianshuo Zhou , David H. Mathews , Liang Huang

RNA design aims to identify RNA sequences that fold into a target secondary structure. This task is challenging in terms of computational efficiency. Most existing methods focus on either minimum free energy (MFE)-based or ensemble-based…

Biomolecules · Quantitative Biology 2026-03-04 Tianshuo Zhou , David H. Mathews , Liang Huang

RNA design, the task of finding a sequence that folds into a target secondary structure, has broad biological and biomedical impact but remains computationally challenging due to the exponentially large sequence space and exponentially many…

Machine Learning · Computer Science 2026-02-16 Milan Gautam , Ning Dai , Tianshuo Zhou , Bowen Xie , David Mathews , Liang Huang

Messenger RNA (mRNA) vaccines are being used for COVID-19, but still suffer from the critical issue of mRNA instability and degradation, which is a major obstacle in the storage, distribution, and efficacy of the vaccine. Previous work…

Motivation: RNA design aims to find RNA sequences that fold into a given target secondary structure, a problem also known as RNA inverse folding. However, not all target structures are designable. Recent advances in RNA designability have…

Data Structures and Algorithms · Computer Science 2026-04-28 Tianshuo Zhou , David H. Mathews , Liang Huang

Designing RNA molecules has garnered recent interest in medicine, synthetic biology, biotechnology and bioinformatics since many functional RNA molecules were shown to be involved in regulatory processes for transcription, epigenetics and…

Machine Learning · Computer Science 2019-04-15 Frederic Runge , Danny Stoll , Stefan Falkner , Frank Hutter

Messenger RNA (mRNA) vaccines and therapeutics are emerging as powerful tools against a variety of diseases, including infectious diseases and cancer. The design of mRNA molecules, particularly the untranslated region (UTR) and coding…

Biomolecules · Quantitative Biology 2024-10-29 Yang Liu , Jie Gao , Xiaonan Zhang , Xiaomin Fang

While RNA technologies hold immense therapeutic potential in a range of applications from vaccination to gene editing, the broad implementation of these technologies is hindered by the challenge of delivering these agents effectively. Lipid…

Biomolecules · Quantitative Biology 2023-08-30 Daisy Yi Ding , Yuhui Zhang , Yuan Jia , Jiuzhi Sun

Solving the RNA inverse folding problem is a critical prerequisite to RNA design, an emerging field in bioengineering with a broad range of applications from reaction catalysis to cancer therapy. Although significant progress has been made…

Quantitative Methods · Quantitative Biology 2019-03-07 Jade Shi , Rhiju Das , Vijay S. Pande

Messenger RNA (mRNA) sequences as therapeutics require optimized design to ensure efficient translation, structural stability, and minimal immunogenicity. This study presents a two-stage in-silico framework that integrates deep learning and…

Computation and Language · Computer Science 2026-05-28 Dhawa Sang Dong , Mausam Gurung , Suraj Kandel

mRNA technology has revolutionized vaccine development, protein replacement therapies, and cancer immunotherapies, offering rapid production and precise control over sequence and efficacy. However, the inherent instability of mRNA poses…

Biomolecules · Quantitative Biology 2025-03-26 Max Ward , Mary Richardson , Mihir Metkar

RNA design is the search for a sequence or set of sequences that will fold into predefined structures, also known as the inverse problem of RNA folding. While numerous RNA design methods have been invented to find sequences capable of…

Biomolecules · Quantitative Biology 2024-08-13 Tianshuo Zhou , Wei Yu Tang , David H. Mathews , Liang Huang

We initiate a study of a query-driven approach to designing partition trees for range-searching problems. Our model assumes that a data structure is to be built for an unknown query distribution that we can access through a sampling oracle,…

Data Structures and Algorithms · Computer Science 2025-02-20 Dimitris Fotakis , Andreas Kalavas , Ioannis Psarros

Rising costs in recent years of developing new drugs and treatments have led to extensive research in optimization techniques in biomolecular design. Currently, the most widely used approach in biomolecular design is directed evolution,…

Machine Learning · Computer Science 2021-11-09 Alexander Whatley , Zhekun Luo , Xiangru Tang

It has been shown that minimum free energy structure for RNAs and RNA-RNA interaction is often incorrect due to inaccuracies in the energy parameters and inherent limitations of the energy model. In contrast, ensemble based quantities such…

Biomolecules · Quantitative Biology 2013-01-09 Hamidreza Chitsaz , Elmirasadat Forouzmand , Gholamreza Haffari

RNA secondary structure prediction is widely used to understand RNA function. Recently, there has been a shift away from the classical minimum free energy (MFE) methods to partition function-based methods that account for folding ensembles…

Biomolecules · Quantitative Biology 2024-02-08 He Zhang , Liang Zhang , David H. Mathews , Liang Huang

RNA design consists of discovering a nucleotide sequence that folds into a target secondary structure. It is useful for synthetic biology, medicine, and nanotechnology. We propose Montparnasse, a Multi Objective Generalized Nested Rollout…

Artificial Intelligence · Computer Science 2025-05-06 Tristan Cazenave

Artificial RNA molecules with novel functionality have many applications in synthetic biology, pharmacy and white biotechnology. The de novo design of such devices using computational methods and prediction tools is a resource-efficient…

Biomolecules · Quantitative Biology 2019-05-13 Stefan Hammer , Christian Günzel , Mario Mörl , Sven Findeiß

In this work, we consider the Combinatorial RNA Design problem, a minimal instance of the RNA design problem which aims at finding a sequence that admits a given target as its unique base pair maximizing structure. We provide complete…

Quantitative Methods · Quantitative Biology 2015-06-22 Jozef Haleš , Ján Maňuch , Yann Ponty , Ladislav Stacho
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