Making the Next Generation of Therapeutics: mRNA Meets Synthetic Biology

Hınçer, Ahmet; Ahan, Recep Erdem; Aras, Ebru; Şeker, Urartu Özgür Şafak

doi:10.1021/acssynbio.3c00253

Cited by 4 publications

(2 citation statements)

References 93 publications

(179 reference statements)

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“…When AlphaFold achieved near-perfect protein fold predictions, it was the most important moment for AI in science so far, yet left plenty of work for structural biology (Perrakis and Sixma, 2021), including the application of coiled coils as a self-assembly building block in synthetic biology (Woolfson, 2023). Similarly, when the mRNA platform became a successful vehicle for a COVID-19 vaccine that Frontiers in Bioengineering and Biotechnology frontiersin.org changed the world, this happened in vitro, yet, the production of synthetic mRNA (Hınçer et al, 2023) or miRNA (Matsuyama and Suzuki, 2019) in the cell itself would be an even more significant breakthrough-and getting there might require the use of AI (Naderi Yeganeh et al, 2023).…”

Section: The Impact Of Ai-enabled Synthetic Biologymentioning

confidence: 99%

The whack-a-mole governance challenge for AI-enabled synthetic biology: literature review and emerging frameworks

Undheim

2024

Front. Bioeng. Biotechnol.

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AI-enabled synthetic biology has tremendous potential but also significantly increases biorisks and brings about a new set of dual use concerns. The picture is complicated given the vast innovations envisioned to emerge by combining emerging technologies, as AI-enabled synthetic biology potentially scales up bioengineering into industrial biomanufacturing. However, the literature review indicates that goals such as maintaining a reasonable scope for innovation, or more ambitiously to foster a huge bioeconomy do not necessarily contrast with biosafety, but need to go hand in hand. This paper presents a literature review of the issues and describes emerging frameworks for policy and practice that transverse the options of command-and-control, stewardship, bottom-up, and laissez-faire governance. How to achieve early warning systems that enable prevention and mitigation of future AI-enabled biohazards from the lab, from deliberate misuse, or from the public realm, will constantly need to evolve, and adaptive, interactive approaches should emerge. Although biorisk is subject to an established governance regime, and scientists generally adhere to biosafety protocols, even experimental, but legitimate use by scientists could lead to unexpected developments. Recent advances in chatbots enabled by generative AI have revived fears that advanced biological insight can more easily get into the hands of malignant individuals or organizations. Given these sets of issues, society needs to rethink how AI-enabled synthetic biology should be governed. The suggested way to visualize the challenge at hand is whack-a-mole governance, although the emerging solutions are perhaps not so different either.

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Section: The Impact Of Ai-enabled Synthetic Biologymentioning

confidence: 99%

The whack-a-mole governance challenge for AI-enabled synthetic biology: literature review and emerging frameworks

Undheim

2024

Front. Bioeng. Biotechnol.

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“…Messenger RNA (mRNA) based therapeutics and vaccines present a promising new platform for the delivery of immunogenic compounds for vaccination or therapeutic proteins for disease treatment and management [1][2][3][4] . While there was recently great success with the rapid development of an mRNA based vaccine for SARS-Cov-2, obstacles still remain to the development of mRNA based therapies, which typically require much higher levels of the therapeutic proteins to be delivered to the target cell 1 .…”

Section: Introductionmentioning

confidence: 99%

Design of a self-regulating mRNA gene circuit

Dykeman

2024

Preprint

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Protein expression from mRNA in vivo is predominately controlled via regulatory feedback mechanisms that adjust the level of mRNA transcription. However, for positive sense single-stranded RNA viruses, protein expression is often controlled via secondary structural elements, such as internal ribosomal entry sites, that are encoded within the mRNA. The self-regulation of mRNA translation observed in this class of viruses suggests that it may be possible to design mRNAs that self-regulate their protein expression, enabling the creation of mRNAs for vaccines and other synthetic biology applications where protein levels in the cell can be tightly controlled without feedback to a transcriptional mechanism. As a proof of concept, I design a polycistronic mRNA based on bacteriophage MS2, where the upstream gene is capable of repressing synthesis of the downstream gene. Using a computational tool that simulates ribosome kinetics and the co-translational folding of the mRNA in response, I show that mutations to the mRNA can be identified which enhance the efficiency of the translation and the repression of the downstream gene. The results of this study open up the possibility of designing bespoke mRNA gene circuits in which the amount of protein synthesised in cells are self-regulated for therapeutic or antigenic purposes.

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