Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Delivery of Therapeutics Using Bacteriophage Vectors

Version 1 : Received: 1 February 2024 / Approved: 5 February 2024 / Online: 5 February 2024 (12:21:04 CET)

How to cite: Venkataraman, S.; Shahgolzari, M.; Yavari, A.; Hefferon, K. Delivery of Therapeutics Using Bacteriophage Vectors. Preprints 2024, 2024020284. https://doi.org/10.20944/preprints202402.0284.v1 Venkataraman, S.; Shahgolzari, M.; Yavari, A.; Hefferon, K. Delivery of Therapeutics Using Bacteriophage Vectors. Preprints 2024, 2024020284. https://doi.org/10.20944/preprints202402.0284.v1

Abstract

Bacteriophages are viruses obligately infecting bacteria. They constitute the most numerous categories of biological forms populating our biosphere and are highly diverse and capable of infecting almost all bacteria. Phages make use of their host cell molecular machinery to express their own genes as they lack the ability to independently reproduce themselves. The inimitable characteristics of bacteriophages have enabled them to become propitious tools in biotechnology and genetic engineering. Phages show no tropism for mammalian cells but however, can be easily modified to present targeting ligands on their surface as coat protein fusions without any negative impacts on phage structure. These displayed ligands thereupon guide the recognition, interaction, and internalization of the phage into cells wherein efficiency of transfection is directly influenced by the copy number of the ligands used for targeting. Engineered phages are more efficacious for transgene delivery and gene expression in cancer cells when compared to other non-viral gene transfer strategies and are therefore being employed in developing cancer vaccines. The high level of stability as well as resistance of bacteriophages to various environmental conditions have enabled the development of virus-like particles (VLPs) capable of successful deliverance of several therapeutic drug cargos into tumors by selective targeting. Phage display technology has been used in therapy of Alzheimer’s disease and drug delivery into the brain. Exogenous peptides fused into the coat protein of phages enables the display of these peptides on the phage surface to generate combinatorial phage that facilitates their rapid separation using their ability to bind to a specific molecular target. Phage therapy has been shown to be safe in clinical settings when compared to antibiotics as it shows no adverse anaphylaxis nor adverse effects such as the emergence of multi-drug resistant bacteria. This review provides intriguing details of the use of natural and engineered phages in the therapy of diseases such as cancer, bacterial infections, bovine mastitis and dementia in addition to the use of CRISPR-Cas9 technology in generating genetically engineered phages. Further, the use of phage display technology in generating monoclonal antibodies against various human diseases is elucidated.

Keywords

Phage display, phage therapy, infectious diseases, mAbs, cancer, theranostics, Alzhiemer’s disease, CRISPR-Cas9 system.

Subject

Biology and Life Sciences, Biology and Biotechnology

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