SMV1, an extremely stable thermophilic virus platform for nanoparticle trafficking in the mammalian GI tract

Abstract

Aims Analysis of the stability and safety of Sulfolobus monocaudavirus 1 (SMV1) during passage through the mammalian GI tract. Methods and Results A major challenge of using nano-vectors to target gut microbiome is their survival during passage through the extremely acidic and proteolytic environment of the mammalian GI tract. Here, we investigated the thermo-acidophilic archaeal virus SMV1 as a candidate therapeutic nano-vector for the distal mammalian GI tract microbiome. We investigated the anatomical distribution, vector stability and immunogenicity of this virus following oral ingestion in mice and compared these traits to the more classically used Inovirus vector M13KE. We found that SMV1 particles were highly stable under both simulated GI tract conditions (in vitro) and in mice (in vivo). Moreover, SMV1 could not be detected in tissues outside the GI tract and it elicited a nearly undetectable inflammatory response. Finally, we used human intestinal organoids (HIOs) to show that labelled SMV1 did not invade or otherwise perturb the human GI tract epithelium. Conclusion Sulfolobus monocaudavirus 1 appeared stable and safe during passage though the mammalian GI tract. Significance and Impact of the Study This is the first study evaluating an archaeal virus as a potential therapeutic nanoparticle delivery system and it opens new possibilities for future development of novel nanoplatforms.

Construction of a Fusellovirus with a Minimal Set of Genes

“…Archaeal viruses, for example, Sulfolobus monocaudavirus 1 (SMV1) and Sulfolobus tengchongenesis spindle-shaped virus 1 (STSV1), have been investigated for potential use as a vector for drug or gene delivery or a nanoparticle in nanobiotechnology . Given their extraordinary stability under harsh conditions, SSV22 and its major capsid protein VP1 may potentially be used in the development of therapeutic nanoparticles for delivering oral drugs targeting the human gut microbiome.…”

“…Most of these archaeal viruses are found in acidic hot springs around the globe and are highly stable at high temperature (e.g., >75 °C) and low pH (e.g., <3.5). Because of these characteristics and the ability of their capsid protein to self-assemble into virus-like particles, these viruses are potentially useful in the development of gut-targeting therapeutic nanoparticle delivery systems capable of overcoming the extremely acidic and proteolytic environment of the mammalian gastrointestinal tract during drug passage. , …”

“…Because of these characteristics and the ability of their capsid protein to self-assemble into virus-like particles, these viruses are potentially useful in the development of gut-targeting therapeutic nanoparticle delivery systems capable of overcoming the extremely acidic and proteolytic environment of the mammalian gastrointestinal tract during drug passage. 1,2 Four families have been established for the spindle-shaped viruses, that is, Fuselloviridae, Bicaudaviridae, Halspiviridae, and Thaspiviridae, 3 among which members of the Fuselloviridae family are the most abundant. 4 A total of 49 fuselloviruses, which primarily infect hyperthermophilic crenarchaea, have been isolated or predicted from virus sequences integrated in the host genomes.…”

Bacteriophages of Thermophilic ‘Bacillus Group’ Bacteria—A Systematic Review, 2023 Update

“…Another health-related application includes the potential for the construction of novel types of vaccine nanocarriers and drug delivery vehicles by employing SMV1 coat protein from unclassified Bicaudaviridae SMV1, infecting Sulfolobus monocaudavirus . The protein has shown in vivo stability without inflammatory response in mice and human intestinal organoids [ 58 ]. Thermophilic or thermotolerant bacteriophages may be used to control bacterial contaminants, including both high- and moderate-temperature food processing environments.…”

Mechanical tomography of an archaeal lemon-shaped virus reveals membrane-like fluidity of the capsid and liquid nucleoprotein cargo

“…Understanding the properties of the lemon-shaped virions is of great interest not only from a fundamental point of view but also from a biotechnological perspective and could stimulate the development of next-generation biomaterials for biomedicine and nanotechnology. Indeed, SMV1 particles have already shown promise as potential nanocarriers ( 21 ).…”