Format

Send to

Choose Destination
Biomaterials. 2015 Jul;58:103-11. doi: 10.1016/j.biomaterials.2015.04.033. Epub 2015 May 11.

Influence of molecular weight upon mannosylated bio-synthetic hybrids for targeted antigen presenting cell gene delivery.

Author information

1
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
2
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA. Electronic address: blainepf@buffalo.edu.

Abstract

Given the rise of antibiotic resistant microbes, genetic vaccination is a promising prophylactic strategy that enables rapid design and manufacture. Facilitating this process is the choice of vector, which is often situationally-specific and limited in engineering capacity. Furthermore, these shortcomings are usually tied to an incomplete understanding of the structure-function relationships driving vector-mediated gene delivery. Building upon our initial report of a hybrid bacterial-biomaterial gene delivery vector, a comprehensive structure-function assessment was completed using a class of mannosylated poly(beta-amino esters). Through a top-down screening methodology, an ideal polymer was selected on the basis of gene delivery efficacy and then used for the synthesis of a stratified molecular weight polymer library. By eliminating contributions of polymer chemical background, we were able to complete an in-depth assessment of gene delivery as a function of (1) polymer molecular weight, (2) relative mannose content, (3) polymer-membrane biophysical properties, (4) APC uptake specificity, and (5) serum inhibition. In summary, the flexibility and potential of the hybrid design featured in this work highlights the ability to systematically probe vector-associated properties for the development of translational gene delivery candidates.

KEYWORDS:

Antigen presenting cells; Bactofection; Cationic polymers; Gene therapy; Nonviral vector

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center