Engineered bacteria as drug delivery vehicles: Principles and prospects

Zhou, Yuxi; Han, Yong Chol

doi:10.1016/j.engmic.2022.100034

Cited by 25 publications

(13 citation statements)

References 138 publications

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“…Ongoing research efforts are underway to further develop nucleic acid delivery and targeting as well as bacterial delivery systems [81,[83][84][85]. We are currently optimizing SVC1 as a platform for the production (via bacterial transcription) and delivery of both linear and circular eukaryote-translatable mRNAs and for the production and delivery of gene editing proteins and RNAs (i.e., CRISPR/Cas machinery).…”

Section: Discussionmentioning

confidence: 99%

An optimized live bacterial delivery vehicle safely and efficaciously delivers bacterially transcribed therapeutic nucleic acids

Mora¹,

Cox²,

Magunda

et al. 2023

Engineering in Life Sciences

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There is an unmet need for delivery platforms that realize the full potential of next‐generation nucleic acid therapeutics. The in vivo usefulness of current delivery systems is limited by numerous weaknesses, including poor targeting specificity, inefficient access to target cell cytoplasm, immune activation, off‐target effects, small therapeutic windows, limited genetic encoding and cargo capacity, and manufacturing challenges. Here we characterize the safety and efficacy of a delivery platform comprising engineered live, tissue‐targeting, non‐pathogenic bacteria (Escherichia coli SVC1) for intracellular cargo delivery. SVC1 bacteria are engineered to specifically bind to epithelial cells via a surface‐expressed targeting ligand, to allow escape of their cargo from the phagosome, and to have minimal immunogenicity. We describe SVC1's ability to deliver short hairpin RNA (shRNA), localized SVC1 administration to various tissues, and its minimal immunogenicity. To validate the therapeutic potential of SVC1, we used it to deliver influenza‐targeting antiviral shRNAs to respiratory tissues in vivo. These data are the first to establish the safety and efficacy of this bacteria‐based delivery platform for use in multiple tissue types and as an antiviral in the mammalian respiratory tract. We expect that this optimized delivery platform will enable a variety of advanced therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

An optimized live bacterial delivery vehicle safely and efficaciously delivers bacterially transcribed therapeutic nucleic acids

Mora¹,

Cox²,

Magunda

et al. 2023

Engineering in Life Sciences

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“…To tackle these problems, we need to choose bacterial strains for engineering wisely, for example, some probiotics present in the human body including E. coli, L. lactis and some yeasts, are more suitable for bacteria-based strategies. 87,88 Designing the bacteria to survive in specific tissues or organs through genetic modifications, or using nanotechnology to engineer inanimate bacterial components, could minimize these problems. Genetic modification can also endow bacterial therapeutics with limited lifespan and responsiveness towards tumor-associated molecules or exogenous signals, and further increase their safety.…”

Section: Biomaterials Science Reviewmentioning

confidence: 99%

Engineered bacteria for augmentedin situtumor vaccination

et al. 2023

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“…6 Though, safety considerations and alternative approaches are crucial aspects to address in the development of these systems. 1,2…”

Section: Introductionmentioning

confidence: 99%

“…Harnessing the unique potential of these modified microorganisms holds promise for improved site-specific drug release, addressing a host of challenges associated with conventional drug delivery methods. [1][2][3] For instance, genetically engineered Salmonella was developed using three genetic circuits to specifically adjust protein release, cell invasion, and drug production. 4 Other studies have used genetically engineered oncolytic bacteria for targeted drug delivery, which have unique properties that cannot be achieved by traditional therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

“…6 Though, safety considerations and alternative approaches are crucial aspects to address in the development of these systems. 1,2 In recent decades, researchers investigated a great number of bacterial strains as potential therapeutic delivery systems, and it has been revealed that GEB have exceptional and comprehensive therapeutic effects in comparison to conventional techniques for preventing and treating certain diseases. [7][8][9][10] Recent scientific developments have led to the emergence of more advanced methods for designing drug delivery systems with precise targeting abilities.…”

Section: Introductionmentioning

confidence: 99%

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