ABSTRACT
Emerging viral diseases, such as Ebola, SARS, MERS, and the pathogen causing COVID-19, SARS-CoV-2, present a challenge for the development of therapeutics because of strict biosafety handling procedures and rapid mutation of their genomes. To facilitate the development of an adaptable and testable therapeutic model system, a colostrum exosome-based nanoparticle delivery system, EPM (exosome-PEI matrix), that overcomes stringent biosafety containment, was used to mimic the expression of viral proteins. This system would greatly expand the number of laboratories actively participating in the screening of potential therapeutics. EPM technology can deliver both plasmid DNA and siRNA to both simulate viral gene expression and screen potential antiviral siRNA therapeutics. Using this nanoplatform, three key SARS-CoV-2 proteins (the spike glycoprotein, nucleocapsid, and replicase) were expressed in vitro and in vivo. In vitro, several viral gene-targeting siRNAs were screened to determine knockdown efficiency, with some siRNA duplexes resulting in 80%-95% knockdown of corresponding protein expression. Moreover, in vivo experiments introducing the spike protein and nucleocapsid by EPM resulted in the production of antibodies against the viral antigen, measured up to 45 d after target delivery. Together, these findings support the efficacy of the EPM delivery system to establish a model for screening antiviral therapeutics-reduced biosafety level.
ABSTRACT
The connection between indigenous peoples and Country (a multidimensional concept including land and water) enabled communities to thrive and survive over millennia. This has been eroded by colonisation, dispossession and increasing food and water insecurity due to climate change and supply constraints. Globally, indigenous peoples experience a disproportionate burden of chronic disease and poor nutrition is a major risk factor. Indigenous leaders have been advocating for community-led solutions. The primary aim of this systematic review is to determine what community-led programs have been undertaken to address food and/or water security globally. A comprehensive search of peer-reviewed literature will be performed in EMBASE, CINAHL, PsycINFO, PubMed, Scopus, LILACs, Informit and Business Source Premier. The grey literature search will include grey literature databases, customised Google search engines, targeted websites, and consultation with experts. The search strategy will consist of four concepts, combined as follows: (1) indigenous peoples AND (2) community program AND (3) food security OR (4) water security. Covidence will be used for study screening and data extraction by two authors. A deductive thematic analysis using indigenous-informed methodologies will be used to synthesise data. This review seeks to provide insight on models and mechanisms to encourage action and metrics for quantifying success of indigenous community-led programs to improve food and water security.