title: Poly-beta amino ester-containing microparticles enhance the activity of nonviral genetic vaccines.
abstract: Current nonviral genetic vaccine systems are less effective than viral vaccines, particularly in cancer systems where epitopes can be weakly immunogenic and antigen-presenting cell processing and presentation to T cells is down-regulated. A promising nonviral delivery method for genetic vaccines involves microencapsulation of antigen-encoding DNA, because such particles protect plasmid payloads and target them to phagocytic antigen-presenting cells. However, conventional microparticle formulations composed of poly lactic-co-glycolic acid take too long to release encapsulated payload and fail to induce high levels of target gene expression. Here, we describe a microparticle-based DNA delivery system composed of a degradable, pH-sensitive poly-beta amino ester and poly lactic-co-glycolic acid. These formulations generate an increase of 3-5 orders of magnitude in transfection efficiency and are potent activators of dendritic cells in vitro. When used as vaccines in vivo, these microparticle formulations, unlike conventional formulations, induce antigen-specific rejection of transplanted syngenic tumor cells.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Little
authors.forename: David M
authors.initials: DM
authors.lastname: Lynn
authors.forename: Qing
authors.initials: Q
authors.lastname: Ge
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
authors.forename: Sidharth V
authors.initials: SV
authors.lastname: Puram
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
authors.forename: Herman N
authors.initials: HN
authors.lastname: Eisen
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods*; D004952:Esters / Q000737:chemistry*; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D006016:Glycolates / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology; D010879:Piperazines / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D014162:Transfection / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D004952:Esters; D006016:Glycolates; D010879:Piperazines; D011091:Polyesters; D011108:Polymers; D019444:Vaccines, DNA; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid