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project revsynbio
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maalvarezl committed Jan 26, 2024
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Expand Up @@ -11,7 +11,7 @@ summary: "This project explores the synergy between synthetic biology and AI to

Synthetic biology is a multidisciplinary field applying engineering principles to the rational design of living systems. Engineering biology can offer fundamental biological insights unattainable through traditional means, and provide new-to-nature functionalities for applications in biotechnology. The synthetic biology workflow of “Design, Build, Test and Learn” (DBTL) reflects the iterative nature of engineering living systems for which genomic data is incomplete for even the simplest organisms1, and often involves trial and error due to the complex nature of living systems.

A workflow to engineer organisms meets manufacturing challenges at each stage. Chemical DNA synthesis is limited to short oligonucleotides due to errors and yield declines inherent to the chemistry2. Sequence features such as repeats, secondary structure, and high %GC content are difficult to synthesise accurately. Synthesis providers have specific constraints and proprietary screening services, and submitting sequences for synthesis could entail rejection and recoding (where possible), time delays, or price premiums. Synthesis providers often provide tools to optimize codon usage for expression in a given organism, yet recoding non-coding DNA, which may harbour regulatory functionality, is hence unpredictable.
A workflow to engineer organisms meets manufacturing challenges at each stage. Chemical DNA synthesis is limited to short oligonucleotides due to errors and yield declines inherent to the chemistry2. Sequence features such as repeats, secondary structure, and high %GC content are difficult to synthesise accurately. Synthesis providers have specific constraints and proprietary screening services, and submitting sequences for synthesis could entail rejection and recoding (where possible), time delays, or price premiums. Synthesis providers often provide tools to optimize codon usage for expression in a given organism, yet recoding non-coding DNA, which may harbour regulatory functionality, is hence unpredictable.

Different approaches exist to assemble short synthetic DNA into larger constructs3.Quality control, error correction, and integration into the host cell must occur before design specifications have been met, and the phenotypic viability of the final organism assessed. Differences in assembly methods and laboratory capabilities represent challenges to optimization, standardization and reproducibility. Two labs may assemble the same DNA construct through different methods. Sub-optimal methodologies would scale poorly for large manufacturing projects, hence accurate sequence-based prediction of approaches to determine the optimal represents a valuable goal of computer-aided manufacturing for synthetic biology.

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