Membrane lipid coated viral nanoparticles and method of use
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Publication Number
US-11413252-B2
Publication Date
2022-08-16
Expiration Date
Abstract
Disclosed is a nanoparticle comprising an inner core comprising a virus; and an outer surface comprising a cellular membrane derived from a cell, and process of making thereof. The virus is an oncolytic virus and cellular membrane is derived from for example red blood cells.
Core Innovation
The invention relates to making a nanoparticle that includes an inner core comprising a single virus and an outer surface comprising a cellular membrane derived from a blood cell, an adipocyte, a stem cell, an endothelial cell, an exosome, a secretory vesicle, or a synaptic vesicle. The cellular membrane coating is formed using a non-salt water solution, and the mixture is processed by sonication to form a nanoparticle in which the inner core is coated with the outer surface.
The problem addressed is that known approaches using saline/PBS and other membrane-coating conditions fail to successfully coat single oncolytic virus cores, leading to reduced virus detection or loss of coating-associated properties. The described solution positions the coating process around the use of a non-salt, sugar-containing aqueous solution, including sucrose or other sugar solutions, rather than saline/PBS, to enable cellular membrane-derived coating to be achieved.
The coated virus nanoparticles are described in connection with systemic circulation and stealth, and with tumor targeting via EPR. The approach further leverages blood-cell membrane markers such as CD47, CD55, and CD59 associated with the cellular membrane source, and includes support by virus detection assay (sandwich ELISA) and measurements using TEM and dynamic light scattering (DLS), including evidence that coating can be lost under alternative methods and regained after de-coating.
Claims Coverage
The document includes one independent process claim with a set of dependent claims that specify additional inventive features, including the non-salt water solution as a sugar solution, the virus as an oncolytic virus, representative oncolytic virus types, and the cellular membrane source from particular blood cell types. Overall, the independent claim covers forming a virus-core, cellular-membrane-coated nanoparticle by combining a single virus with a cellular membrane in a non-salt water solution and applying sonication.
Virus core with cellular membrane outer surface in non-salt water solution
A process of making a nanoparticle by combining an inner core comprising a single virus with an outer surface comprising a cellular membrane derived from a blood cell, an adipocyte, a stem cell, an endothelial cell, an exosome, a secretory vesicle or a synaptic vesicle in a non-salt water solution.
Sonication to form a cellular membrane-coated virus nanoparticle
Applying sonication to the mixture to form a nanoparticle comprising the inner core coated with the outer surface.
The claim set centers on forming a nanoparticle by sonication of a mixture containing a single virus core and a cellular-membrane-derived outer surface in a non-salt water solution. The dependent claims narrow the non-salt water solution to sugar solutions and further restrict the virus to oncolytic viruses and specify examples and blood-cell membrane sources.
Stated Advantages
Systemic circulation and stealth.
Tumor targeting via EPR.
Enables cellular membrane-derived coating to be achieved when saline/PBS and other conditions fail to successfully coat single oncolytic virus cores.
Reduced virus detection loss or loss of coating-associated properties is addressed.
Documented Applications
Tumor targeting via EPR.
Systemic circulation.
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