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Mannosylated poly(beta-amino esters) for targeted antigen presenting cell immune modulation

Jones, Charles H; Chen, Mingfu; Ravikrishnan, Anitha; Reddinger, Ryan; Zhang, Guojian; Hakansson, Anders P LU and Pfeifer, Blaine A (2015) In Biomaterials 37. p.44-333
Abstract

Given the rise of antibiotic resistance and other difficult-to-treat diseases, genetic vaccination is a promising preventative approach that can be tailored and scaled according to the vector chosen for gene delivery. However, most vectors currently utilized rely on ubiquitous delivery mechanisms that ineffectively target important immune effectors such as antigen presenting cells (APCs). As such, APC targeting allows the option for tuning the direction (humoral vs cell-mediated) and strength of the resulting immune responses. In this work, we present the development and assessment of a library of mannosylated poly(beta-amino esters) (PBAEs) that represent a new class of easily synthesized APC-targeting cationic polymers. Polymeric... (More)

Given the rise of antibiotic resistance and other difficult-to-treat diseases, genetic vaccination is a promising preventative approach that can be tailored and scaled according to the vector chosen for gene delivery. However, most vectors currently utilized rely on ubiquitous delivery mechanisms that ineffectively target important immune effectors such as antigen presenting cells (APCs). As such, APC targeting allows the option for tuning the direction (humoral vs cell-mediated) and strength of the resulting immune responses. In this work, we present the development and assessment of a library of mannosylated poly(beta-amino esters) (PBAEs) that represent a new class of easily synthesized APC-targeting cationic polymers. Polymeric characterization and assessment methodologies were designed to provide a more realistic physiochemical profile prior to in vivo evaluation. Gene delivery assessment in vitro showed significant improvement upon PBAE mannosylation and suggested that mannose-mediated uptake and processing influence the magnitude of gene delivery. Furthermore, mannosylated PBAEs demonstrated a strong, efficient, and safe in vivo humoral immune response without use of adjuvants when compared to genetic and protein control antigens. In summary, the gene delivery effectiveness provided by mannosylated PBAE vectors offers specificity and potency in directing APC activation and subsequent immune responses.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Antigen-Presenting Cells, Female, Fluorescence, Green Fluorescent Proteins, HeLa Cells, Humans, Immunization, Immunomodulation, Mannose, Mice, Inbred BALB C, Models, Animal, Polymers, Transfection
in
Biomaterials
volume
37
pages
12 pages
publisher
Elsevier
external identifiers
  • scopus:84922227871
ISSN
1878-5905
DOI
10.1016/j.biomaterials.2014.10.037
language
English
LU publication?
no
id
775a6321-4f4f-4c85-b69f-d4244fb54244
date added to LUP
2016-05-20 17:57:20
date last changed
2017-05-21 04:51:08
@article{775a6321-4f4f-4c85-b69f-d4244fb54244,
  abstract     = {<p>Given the rise of antibiotic resistance and other difficult-to-treat diseases, genetic vaccination is a promising preventative approach that can be tailored and scaled according to the vector chosen for gene delivery. However, most vectors currently utilized rely on ubiquitous delivery mechanisms that ineffectively target important immune effectors such as antigen presenting cells (APCs). As such, APC targeting allows the option for tuning the direction (humoral vs cell-mediated) and strength of the resulting immune responses. In this work, we present the development and assessment of a library of mannosylated poly(beta-amino esters) (PBAEs) that represent a new class of easily synthesized APC-targeting cationic polymers. Polymeric characterization and assessment methodologies were designed to provide a more realistic physiochemical profile prior to in vivo evaluation. Gene delivery assessment in vitro showed significant improvement upon PBAE mannosylation and suggested that mannose-mediated uptake and processing influence the magnitude of gene delivery. Furthermore, mannosylated PBAEs demonstrated a strong, efficient, and safe in vivo humoral immune response without use of adjuvants when compared to genetic and protein control antigens. In summary, the gene delivery effectiveness provided by mannosylated PBAE vectors offers specificity and potency in directing APC activation and subsequent immune responses.</p>},
  author       = {Jones, Charles H and Chen, Mingfu and Ravikrishnan, Anitha and Reddinger, Ryan and Zhang, Guojian and Hakansson, Anders P and Pfeifer, Blaine A},
  issn         = {1878-5905},
  keyword      = {Animals,Antigen-Presenting Cells,Female,Fluorescence,Green Fluorescent Proteins,HeLa Cells,Humans,Immunization,Immunomodulation,Mannose,Mice, Inbred BALB C,Models, Animal,Polymers,Transfection},
  language     = {eng},
  pages        = {44--333},
  publisher    = {Elsevier},
  series       = {Biomaterials},
  title        = {Mannosylated poly(beta-amino esters) for targeted antigen presenting cell immune modulation},
  url          = {http://dx.doi.org/10.1016/j.biomaterials.2014.10.037},
  volume       = {37},
  year         = {2015},
}