Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Rapid Development of Animal Models for Infectious Disease Research through Vectorized Receptor Molecule Expression

Version 1 : Received: 26 September 2024 / Approved: 26 September 2024 / Online: 27 September 2024 (11:47:38 CEST)

How to cite: Goens, M. M.; Howard, E. L.; Warner, B. M.; Susta, L.; Wootton, S. K. Rapid Development of Animal Models for Infectious Disease Research through Vectorized Receptor Molecule Expression. Preprints 2024, 2024092154. https://doi.org/10.20944/preprints202409.2154.v1 Goens, M. M.; Howard, E. L.; Warner, B. M.; Susta, L.; Wootton, S. K. Rapid Development of Animal Models for Infectious Disease Research through Vectorized Receptor Molecule Expression. Preprints 2024, 2024092154. https://doi.org/10.20944/preprints202409.2154.v1

Abstract

The emergence and re-emergence of pathogens with pandemic potential has been a persistent issue throughout history. Recent decades have seen significant outbreaks of zoonotic viruses from members of the Coronaviridae, Filoviridae, Paramyxoviridae, Flaviviridae, and Togaviridae families, resulting in widespread infections. The continual emergence of zoonotic viral pathogens and associated infections highlights the need for prevention strategies and effective treatments. Central to this effort is the availability of suitable animal models, which are essential for understanding pathogenesis and assessment of transmission dynamics. These animals are also critical for evaluating the safety and efficacy of novel vaccines or therapeutics and are essential in facilitating regulatory approval of new products. Rapid development of animal models is an integral aspect of pandemic response and preparedness; however, their establishment is fraught by several rate-limiting steps, including selection of a suitable species, the logistical challenges associated with sharing and disseminating transgenic animals (e.g., the time-intensive nature of breeding and maintaining colonies), availability of technical expertise, as well as ethical and regulatory approvals. A method for rapid development of relevant animal models that has recently gained traction is the use of gene therapy vectors to express human viral receptors in readily accessible laboratory animals to enable virus infection and development of clinical disease. These models can be developed rapidly on any genetic background making mechanistic studies and accelerated evaluation of novel countermeasures possible. In this review, we will discuss important considerations for the effective development of animal models using viral vector approaches and review the current vector-based animal models for studying viral pathogenesis and evaluating prophylactic and therapeutic strategies.

Keywords

adeno-associated virus vector; animal models; zoonotic infections; pandemic potential; viral countermeasures; prophylactic and therapeutic strategies

Subject

Biology and Life Sciences, Virology

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