Abstract: A construct includes a core comprising an external surface and a plurality of pores, a cargo disposed in a pore of the plurality of pores, the cargo comprising a CRISPR Cas9 component or a nucleic acid sequence encoding a CRISPR Cas9 component; and a coating coupled to the core, wherein the coating comprises a cationic lipid, a pegylated lipid, a zwitterionic lipid, and a sterol. The coating may comprise a molar ratio of about 1 cationic lipid to 1 zwitterionic lipid to 0.9 sterol to 0.15 PEGylated lipid, wherein each molar ratio optionally varies by about plus or minus 10%. A method of treatment is also provided.

Abstract: An in vitro assay was designed to measure the activity of the alphavirus non-structural protein 2 (nsP2), which is the viral protease and is required for viral replication. By taking advantage of fluorescence-resonance energy transfer between two proteins, a protease cleavage assay was generated. This was utilized for high-throughput screening of 40,000 small molecules. Inhibitors were validated using cell-based assays to measure alphavirus infection and cytotoxicity. Certain compounds were then characterized for anti-viral efficacy in various cell lines in numerous assays. Compounds were tested against Chikungunya virus, Venezuelan Equine Encephalitis virus, Rift Valley Fever virus, and Zika virus. Three compounds (compounds I, II, and III) showed pan-alphavirus anti-viral efficacy at concentrations that did not result in cell toxicity. An additional compound, structure IV, showed broad spectrum inhibition of all viruses tested.

Abstract: A construct includes a core comprising an external surface and a plurality of pores, a cargo disposed in a pore of the plurality of pores, the cargo comprising a CRISPR Cas9 component or a nucleic acid sequence encoding a CRISPR Cas9 component; and a coating coupled to the core, wherein the coating comprises a cationic lipid, a pegylated lipid, a zwitterionic lipid, and a sterol. The coating may comprise a molar ratio of about 1 cationic lipid to 1 zwitterionic lipid to 0.9 sterol to 0.15 PEGylated lipid, wherein each molar ratio optionally varies by about plus or minus 10%. A method of treatment is also provided.

Abstract: The present invention relates to a construct including a porous core, a cargo, and a spacer disposed between the core and the cargo. In some examples, the construct further includes an outer layer composed of a lipid, a polymer, or a combination thereof. Methods of making and employing such constructs are also described herein.