Advanced

Hybrid biosynthetic gene therapy vector development and dual engineering capacity

Jones, Charles H; Ravikrishnan, Anitha; Chen, Mingfu; Reddinger, Ryan; Kamal Ahmadi, Mahmoud; Rane, Snehal; Hakansson, Anders P LU and Pfeifer, Blaine A (2014) In Proceedings of the National Academy of Sciences 111(34). p.5-12360
Abstract

Genetic vaccines offer a treatment opportunity based upon successful gene delivery to specific immune cell modulators. Driving the process is the vector chosen for gene cargo packaging and subsequent delivery to antigen-presenting cells (APCs) capable of triggering an immune cascade. As such, the delivery process must successfully navigate a series of requirements and obstacles associated with the chosen vector and target cell. In this work, we present the development and assessment of a hybrid gene delivery vector containing biological and biomaterial components. Each component was chosen to design and engineer gene delivery separately in a complimentary and fundamentally distinct fashion. A bacterial (Escherichia coli) inner core and... (More)

Genetic vaccines offer a treatment opportunity based upon successful gene delivery to specific immune cell modulators. Driving the process is the vector chosen for gene cargo packaging and subsequent delivery to antigen-presenting cells (APCs) capable of triggering an immune cascade. As such, the delivery process must successfully navigate a series of requirements and obstacles associated with the chosen vector and target cell. In this work, we present the development and assessment of a hybrid gene delivery vector containing biological and biomaterial components. Each component was chosen to design and engineer gene delivery separately in a complimentary and fundamentally distinct fashion. A bacterial (Escherichia coli) inner core and a biomaterial [poly(beta-amino ester)]-coated outer surface allowed the simultaneous application of molecular biology and polymer chemistry to address barriers associated with APC gene delivery, which include cellular uptake and internalization, phagosomal escape, and intracellular cargo concentration. The approach combined and synergized normally disparate vector properties and tools, resulting in increased in vitro gene delivery beyond individual vector components or commercially available transfection agents. Furthermore, the hybrid device demonstrated a strong, efficient, and safe in vivo humoral immune response compared with traditional forms of antigen delivery. In summary, the flexibility, diversity, and potential of the hybrid design were developed and featured in this work as a platform for multivariate engineering at the vector and cellular scales for new applications in gene delivery immunotherapy.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Antigen-Presenting Cells, Cell Line, Escherichia coli, Female, Gene Transfer Techniques, Genetic Engineering, Genetic Therapy, Genetic Vectors, Immunization, Mice, Mice, Inbred BALB C, Models, Animal, Ovalbumin, Vaccines, DNA
in
Proceedings of the National Academy of Sciences
volume
111
issue
34
pages
6 pages
publisher
National Academy of Sciences
external identifiers
  • Scopus:84906707843
ISSN
1091-6490
DOI
10.1073/pnas.1411355111
language
English
LU publication?
yes
id
9083cd32-4c24-455a-b3f1-80d78ae05bda
date added to LUP
2016-05-21 10:46:21
date last changed
2017-01-01 08:26:42
@article{9083cd32-4c24-455a-b3f1-80d78ae05bda,
  abstract     = {<p>Genetic vaccines offer a treatment opportunity based upon successful gene delivery to specific immune cell modulators. Driving the process is the vector chosen for gene cargo packaging and subsequent delivery to antigen-presenting cells (APCs) capable of triggering an immune cascade. As such, the delivery process must successfully navigate a series of requirements and obstacles associated with the chosen vector and target cell. In this work, we present the development and assessment of a hybrid gene delivery vector containing biological and biomaterial components. Each component was chosen to design and engineer gene delivery separately in a complimentary and fundamentally distinct fashion. A bacterial (Escherichia coli) inner core and a biomaterial [poly(beta-amino ester)]-coated outer surface allowed the simultaneous application of molecular biology and polymer chemistry to address barriers associated with APC gene delivery, which include cellular uptake and internalization, phagosomal escape, and intracellular cargo concentration. The approach combined and synergized normally disparate vector properties and tools, resulting in increased in vitro gene delivery beyond individual vector components or commercially available transfection agents. Furthermore, the hybrid device demonstrated a strong, efficient, and safe in vivo humoral immune response compared with traditional forms of antigen delivery. In summary, the flexibility, diversity, and potential of the hybrid design were developed and featured in this work as a platform for multivariate engineering at the vector and cellular scales for new applications in gene delivery immunotherapy.</p>},
  author       = {Jones, Charles H and Ravikrishnan, Anitha and Chen, Mingfu and Reddinger, Ryan and Kamal Ahmadi, Mahmoud and Rane, Snehal and Hakansson, Anders P and Pfeifer, Blaine A},
  issn         = {1091-6490},
  keyword      = {Animals,Antigen-Presenting Cells,Cell Line,Escherichia coli,Female,Gene Transfer Techniques,Genetic Engineering,Genetic Therapy,Genetic Vectors,Immunization,Mice,Mice, Inbred BALB C,Models, Animal,Ovalbumin,Vaccines, DNA},
  language     = {eng},
  month        = {08},
  number       = {34},
  pages        = {5--12360},
  publisher    = {National Academy of Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Hybrid biosynthetic gene therapy vector development and dual engineering capacity},
  url          = {http://dx.doi.org/10.1073/pnas.1411355111},
  volume       = {111},
  year         = {2014},
}