Influence of molecular weight upon mannosylated bio-synthetic hybrids for targeted antigen presenting cell gene delivery.
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.
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
Charles H
CH
Jones
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
Akhila
A
Gollakota
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
Mingfu
M
Chen
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
Tai-Chun
TC
Chung
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
Anitha
A
Ravikrishnan
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
Guojian
G
Zhang
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.
Blaine A
BA
Pfeifer
D000818:Animals; D000938:Antigen-Presenting Cells; D001672:Biocompatible Materials / Q000737:chemistry; D001703:Biophysics; D004926:Escherichia coli / Q000378:metabolism; D004952:Esters; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000737:chemistry*; D051379:Mice; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry; D014162:Transfection
D001672:Biocompatible Materials; D004952:Esters; D011108:Polymers; D008358:Mannose
Antigen presenting cells; Bactofection; Cationic polymers; Gene therapy; Nonviral vector