RNA replicon delivery via lipid-complexed PRINT protein particles.
Herein we report the development of a nonviral lipid-complexed PRINT (particle replication in nonwetting templates) protein particle system (LPP particle) for RNA replicon delivery with a view toward RNA replicon-based vaccination. Cylindrical bovine serum albumin (BSA) particles (diameter (d) 1 μm, height (h) 1 μm) loaded with RNA replicon and stabilized with a fully reversible disulfide cross-linker were fabricated using PRINT technology. Highly efficient delivery of the particles to Vero cells was achieved by complexing particles with a mixture of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) lipids. Our data suggest that (1) this lipid-complexed protein particle is a promising system for delivery of RNA replicon-based vaccines and (2) it is necessary to use a degradable cross-linker for successful delivery of RNA replicon via protein-based particles.
Department of Chemistry, △Department of Pharmacology, ∥UNC Eshelman School of Pharmacy, †Carolina Center of Cancer Nanotechnology Excellence, ⊥Institute for Advanced Materials, #Institute for Nanomedicine, ¶Lineberger Comprehensive Cancer Center, and ■Department of Biochemistry and Biophysics, University of North Carolina , Chapel Hill, North Carolina 27599, United States.
Jing
J
Xu
J Christopher
JC
Luft
Xianwen
X
Yi
Shaomin
S
Tian
Gary
G
Owens
Jin
J
Wang
Ashley
A
Johnson
Peter
P
Berglund
Jonathan
J
Smith
Mary E
ME
Napier
Joseph M
JM
DeSimone
D002460:Cell Line; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D018014:Gene Transfer Techniques; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012313:RNA / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D012710:Serum Albumin, Bovine / Q000737:chemistry
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D012710:Serum Albumin, Bovine; D012313:RNA; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane