INTRO SENTENCE:
UCLA researchers in the Department of Chemistry & Biochemistry have developed novel enveloped virus-like particles for the delivery of cancer vaccines, viral vaccines, and chemically-modified mRNA.
TITLE:
In Vitro Reconstituted Enveloped Virus-Like Particles (EVLPs) For RNA Gene Delivery
BACKGROUND:
Virus-like particles (VLPs) are molecules that mimic the organization and structure of native viruses, but are non-infectious because they lack the viral genome. VLPs are good candidates for an inexpensive and safe delivery system of genes, vaccines, or other therapeutics. Specifically, in vitro reconstituted VLPs from purified products allows for the packing and delivery of self-replicating RNA genes to mammalian cells without the need for cell culture. Other vectors or platforms for gene delivery include RNA-containing liposomes and virosomes. However, these strategies are plagued by problems with stability against aggregation, nucleases, as well as polydispersion, and virosomes also involve potentially dangerous viral envelope components. When VLPs are assembled as nucleocapsids, consisting of a single RNA molecule surrounded by a rigid shell (capsid), they are monodispersed and resistant to both aggregation and RNases. These qualities make VLPs the most attractive platform for RNA gene delivery. Yet, VLP functionalization with ligands, targeting to specific cells, and uptake must be enhanced to allow for the targeted delivery of cancer vaccines, viral vaccines, and miroRNAs for gene therapy.
INNOVATION:
UCLA researchers have wrapped VLPs with a lipid bilayer envelop, to further protect the RNA and disguise it from the immune system. These enveloped virus-like particles (EVLPs) are monodisperse, well-defined, and robust particles that are functionalized for targeting and uptake by mammalian cells. Additionally, EVLPs may be conjugated with polypeptide ligands to further increase specific cell-targeting efficiency. EVLPs are assembled in vitro from purified components, which avoids the introduction of unwanted RNA or proteins during cell culture. This technology may be used to deliver cancer and viral vaccines, chemically-modified mRNA, or various other therapeutics.
POTENTIAL APPLICATIONS:
• Delivery of cancer and viral vaccines in VLP-packaged mRNA form
• Delivery of chemically-modified mRNA in VLP form
• MRI contrast agents
ADVANTAGES:
• EVLPs are monodisperse, protective against aggregation, and are stable against RNases
• Conjugation with polypeptide ligands allows efficient and targeted uptake into specific cells
• In vitro self-assembly of EVLPs from purified components avoids need for cell cultures
• No unwanted RNA or proteins involved due to in vitro assembly
• Lipid bilayer envelop provides enhanced functionalization, targeting, and uptake of VLPs
DEVELOPMENT-TO-DATE:
Enveloped virus-like particles have been synthesized and tested for efficient in vitro assembly.
Related Papers (from the inventors only)
O. Azizgolshani, R. F. Garmann, R. D. Cadena-Nava, C. M. Knobler and W. M. Gelbart, “Reconstituted Plant Viral Capsids Can Release Genes to Mammalian Cells,” Virology 441, 12-17 (2013), also for unwrapped VLPs.