Virus-based therapies have gained momentum as the next generation of treatments for a variety of serious diseases. In order to make these therapies more controllable, stimulus-responsive viral vectors capable of sensing and responding to specific environmental inputs are currently being developed. A number of viruses naturally respond to endogenous stimuli, such as pH, redox, and proteases, which are present at different concentrations in diseases and at different organ and organelle sites. Additionally, rather than relying on natural viral properties, efforts are underway to engineer viruses to respond to endogenous stimuli in new ways as well as to exogenous stimuli, such as temperature, magnetic field, and optical light. Viruses with stimulus-responsive capabilities, either nature-evolved or human-engineered, will be reviewed to capture the current state of the field. Stimulus-responsive viral vector design considerations as well as gaps in current research efforts will be identified.
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http://dx.doi.org/10.1016/j.jconrel.2017.08.021 | DOI Listing |
Nat Commun
April 2024
Laboratory of Organic Chemistry, ETH Zürich, Zürich, Switzerland.
Controlled assembly of a protein shell around a viral genome is a key step in the life cycle of many viruses. Here we report a strategy for regulating the co-assembly of nonviral proteins and nucleic acids into highly ordered nucleocapsids in vitro. By fusing maltose binding protein to the subunits of NC-4, an engineered protein cage that encapsulates its own encoding mRNA, we successfully blocked spontaneous capsid assembly, allowing isolation of the individual monomers in soluble form.
View Article and Find Full Text PDFJ Nanobiotechnology
August 2023
Beijing Key Laboratory of Environmental & Viral Oncology, Faculty of Environment & Life, Beijing University of Technology, Beijing, 100124, China.
Carmustine (BCNU), a vital type of chloroethylnitrosourea (CENU), inhibits tumor cells growth by inducing DNA damage at O position of guanine and eventually forming dG-dC interstrand cross-links (ICLs). However, the clinical application of BCNU is hindered to some extent by the absence of tumor selectivity, poor stability and O-alkylguanine-DNA alkyltransferase (AGT) mediated drug resistance. In recent years, tumor microenvironment has been widely utilized for advanced drug delivery.
View Article and Find Full Text PDFInt J Mol Sci
June 2023
School of Chemistry and Physics, College of Agriculture Engineering and Science, Pietermaritzburg Campus, University of KwaZulu-Natal, Pietermaritzburg 3209, South Africa.
The rapid rise in research and development following the discovery of photodynamic therapy to establish novel photosensitizers and overcome the limitations of the technology soon after its clinical translation has given rise to a few significant milestones. These include several novel generations of photosensitizers, the widening of the scope of applications, leveraging of the offerings of nanotechnology for greater efficacy, selectivity for the disease over host tissue and cells, the advent of combination therapies with other similarly minimally invasive therapeutic technologies, the use of stimulus-responsive delivery and disease targeting, and greater penetration depth of the activation energy. Brought together, all these milestones have contributed to the significant enhancement of what is still arguably a novel technology.
View Article and Find Full Text PDFBiomater Sci
July 2023
Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
Non-viral polymeric vectors with good biocompatibility have been recently explored as delivery systems for clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) nucleases. In this review, based on current limitations and critical barriers, we summarize the advantages of stimulus-responsive polymeric delivery vectors (, pH, redox, or enzymes) towards controllable CRISPR/Cas9 genome editing system delivery as well as the advances in using stimulus-responsive CRISPR/Cas9 polymeric carriers towards cancer treatment. Last but not least, the key challenges and promising development strategies of stimulus-responsive polymeric vector designs for CRISPR/Cas9 systems will also be discussed.
View Article and Find Full Text PDFJ Appl Crystallogr
October 2022
Novosibirsk State University, Pirogova Street 2, Novosibirsk, 630090, Russian Federation.
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