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Enhanced immunostimulatory effects of DNA-encapsulated peptide hydrogels

DNA that encodes tumor-specific antigens represents potential immunostimulatory agents. However, rapid enzymatic degradation and fragmentation of DNA during administration can result in limited vector expression and, consequently, poor efficacy. These challenges have necessitated the use of novel st... Full description

Journal Title: Biomaterials June 2015, Vol.53, pp.545-553
Main Author: Medina, Scott H
Other Authors: Li, Sandra , Howard, O.M. Zack , Dunlap, Micah , Trivett, Anna , Schneider, Joel P , Oppenheim, Joost J
Format: Electronic Article Electronic Article
Language: English
Subjects:
DNA
ID: ISSN: 0142-9612 ; E-ISSN: 1878-5905 ; DOI: 10.1016/j.biomaterials.2015.02.125
Link: https://www.sciencedirect.com/science/article/pii/S014296121500263X
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recordid: elsevier_sdoi_10_1016_j_biomaterials_2015_02_125
title: Enhanced immunostimulatory effects of DNA-encapsulated peptide hydrogels
format: Article
creator:
  • Medina, Scott H
  • Li, Sandra
  • Howard, O.M. Zack
  • Dunlap, Micah
  • Trivett, Anna
  • Schneider, Joel P
  • Oppenheim, Joost J
subjects:
  • DNA
  • Peptide
  • Drug Delivery
  • Self Assembly
  • Gene Expression
  • Medicine
  • Engineering
ispartof: Biomaterials, June 2015, Vol.53, pp.545-553
description: DNA that encodes tumor-specific antigens represents potential immunostimulatory agents. However, rapid enzymatic degradation and fragmentation of DNA during administration can result in limited vector expression and, consequently, poor efficacy. These challenges have necessitated the use of novel strategies for DNA delivery. Herein, we study the ability of cationic self-assembling peptide hydrogels to encapsulate plasmid DNA, and enhance its immunostimulatory potential . The effect of network charge on the gel's ability to retain the DNA was assessed employing three gel-forming peptides that vary systematically in formal charge. The peptide HLT2, having a formal charge of +5 at neutral pH, was optimal in encapsulating microgram quantities of DNA with little effect on its rheological properties, allowing its effective syringe delivery . The plasmid, DNA(TA), encapsulated within these gels encodes for a melanoma-specific gp100 antigen fused to the alarmin protein adjuvant HMGN1. Implantation of DNA(TA)-loaded HLT2 gels into mice resulted in an acute inflammatory response with the presence of polymorphonuclear cells, which was followed by infiltrating macrophages. These cellular infiltrates aid in the processing of encapsulated DNA, promoting increased lymphoproliferation and producing an enhanced immune response mediated by CD4+/IFNγ+ expressing Th1 cells, and complemented by the formation of gp100-specific antibodies.
language: eng
source:
identifier: ISSN: 0142-9612 ; E-ISSN: 1878-5905 ; DOI: 10.1016/j.biomaterials.2015.02.125
fulltext: fulltext
issn:
  • 0142-9612
  • 01429612
  • 1878-5905
  • 18785905
url: Link


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titleEnhanced immunostimulatory effects of DNA-encapsulated peptide hydrogels
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descriptionDNA that encodes tumor-specific antigens represents potential immunostimulatory agents. However, rapid enzymatic degradation and fragmentation of DNA during administration can result in limited vector expression and, consequently, poor efficacy. These challenges have necessitated the use of novel strategies for DNA delivery. Herein, we study the ability of cationic self-assembling peptide hydrogels to encapsulate plasmid DNA, and enhance its immunostimulatory potential . The effect of network charge on the gel's ability to retain the DNA was assessed employing three gel-forming peptides that vary systematically in formal charge. The peptide HLT2, having a formal charge of +5 at neutral pH, was optimal in encapsulating microgram quantities of DNA with little effect on its rheological properties, allowing its effective syringe delivery . The plasmid, DNA(TA), encapsulated within these gels encodes for a melanoma-specific gp100 antigen fused to the alarmin protein adjuvant HMGN1. Implantation of DNA(TA)-loaded HLT2 gels into mice resulted in an acute inflammatory response with the presence of polymorphonuclear cells, which was followed by infiltrating macrophages. These cellular infiltrates aid in the processing of encapsulated DNA, promoting increased lymphoproliferation and producing an enhanced immune response mediated by CD4+/IFNγ+ expressing Th1 cells, and complemented by the formation of gp100-specific antibodies.
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