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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

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

Co-optimizing mRNA sequences for both codon optimality and secondary structure is crucial for producing stable and efficacious mRNA therapeutics. Codon optimization, which adjusts nucleotide sequences to enhance translational efficiency,…

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 tasks of designing RNAs are discrete optimization problems, and several versions of these problems are NP-hard. As an alternative to commonly used local search methods, we formulate these problems as continuous optimization and develop…

Biomolecules · Quantitative Biology 2024-03-04 Ning Dai , Wei Yu Tang , Tianshuo Zhou , David H. Mathews , Liang Huang

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

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

Motivation: Codon optimization of Open Reading Frame (ORF) sequences is essential for enhancing mRNA stability and expression in applications like mRNA vaccines, where codon choice can significantly impact protein yield which directly…

Quantitative Methods · Quantitative Biology 2024-12-17 Shashank Pathak , Guohui Lin

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

The pharmaceutical Research and development (R&D) process is lengthy and costly, taking nearly a decade to bring a new drug to the market. However, advancements in biotechnology, computational methods, and machine learning algorithms have…

Biomolecules · Quantitative Biology 2024-01-24 Damilola Oshunyinka

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

Optimizing the mRNA codon has an essential impact on gene expression for a specific target protein. It is an NP-hard problem; thus, exact solutions to such optimization problems become computationally intractable for realistic problem sizes…

Quantum Physics · Physics 2024-05-13 Hongfeng Zhang , Aritra Sarkar , Koen Bertels

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

We describe a dynamic programming algorithm for predicting optimal RNA secondary structure, including pseudoknots. The algorithm has a worst case complexity of ${\cal O}(N^6)$ in time and ${\cal O}(N^4)$ in storage. The description of the…

Biological Physics · Physics 2009-09-25 Elena Rivas , Sean R. Eddy

We present a detailed study of the performance and reliability of design procedures based on energy minimization. The analysis is carried out for model proteins where exact results can be obtained through exhaustive enumeration. The…

Statistical Mechanics · Physics 2007-05-23 Cristian Micheletti , Amos Maritan

Nucleic acid sequence design via codon optimization is a fundamental task with applications across synthetic biology, mRNA therapeutics, and vaccine design. Given a target protein, it is a major open challenge to navigate the…

Quantitative Methods · Quantitative Biology 2026-04-22 Mark Fornace , Christina Wuyan Wang , Michael Lindsey

Advances in machine learning have enabled the prediction of immune system responses to prophylactic and therapeutic vaccines. However, the engineering task of designing vaccines remains a challenge. In particular, the genetic variability of…

Quantitative Methods · Quantitative Biology 2023-01-30 Zheng Dai , David Gifford

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

RNA design aims to find a sequence that folds with highest probability into a designated target structure. However, certain structures are undesignable, meaning no sequence can fold into the target structure under the default (Turner) RNA…

Data Structures and Algorithms · Computer Science 2025-05-06 Tianshuo Zhou , Wei Yu Tang , Apoorv Malik , David H. Mathews , Liang Huang

Replication of SARS-CoV2 virions is an error-prone process which may eventually generate a percentage of impaired protein copies with complete lack of functionality. For instance, after RNA mis-replication, a very premature stop codon (UAG,…

Genomics · Quantitative Biology 2021-06-08 Alessio D'Alessandro
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