title: Structure-Function Assessment of Mannosylated Poly(β-amino esters) upon Targeted Antigen Presenting Cell Gene Delivery.
abstract: Antigen presenting cell (APC) gene delivery is a promising avenue for modulating immunological outcomes toward a desired state. Recently, our group developed a delivery methodology to elicit targeted and elevated levels of APC-mediated gene delivery. During these initial studies, we observed APC-specific structure-function relationships with the vectors used during gene delivery that differ from current non-APC cell lines, thus, emphasizing a need to re-evaluate vector-associated parameters in the context of APC gene transfer. Thus, we describe the synthesis and characterization of a second-generation mannosylated poly(β-amino ester) library stratified by molecular weight. To better understand the APC-specific structure-function relationships governing polymeric gene delivery, the library was systematically characterized by (1) polymer molecular weight, (2) relative mannose content, (3) polyplex biophysical properties, and (4) gene delivery efficacy. In this library, polymers with the lowest molecular weight and highest relative mannose content possessed gene delivery transfection efficiencies as good as or better than commercial controls. Among this group, the most effective polymers formed the smallest polymer-plasmid DNA complexes (∼300 nm) with moderate charge densities (<10 mV). This convergence in polymer structure and polyplex biophysical properties suggests a unique mode of action and provides a framework within which future APC-targeting polymers can be designed.
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York, United States.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Jones
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York, United States.
authors.forename: Mingfu
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York, United States.
authors.forename: Akhila
authors.initials: A
authors.lastname: Gollakota
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York, United States.
authors.forename: Anitha
authors.initials: A
authors.lastname: Ravikrishnan
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York, United States.
authors.forename: Guojian
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York, United States.
authors.forename: Sharon
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York, United States.
authors.forename: Myles
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York, United States.
authors.forename: Chong
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York, United States.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York, United States.
authors.forename: Blaine A
authors.initials: BA
authors.lastname: Pfeifer
mesh_terms: D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D004247:DNA / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008358:Mannose / Q000737:chemistry; D010957:Plasmids / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D011108:Polymers; C507253:poly(beta-amino ester); D004247:DNA; D008358:Mannose
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