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| Parallel synthesis and biophysical characterization of a degradable polymer library for gene delivery |
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| Author(s): Akinc A, Lynn DM, Anderson DG, Langer R |
| Source: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Volume: 125 Issue: 18 Pages: 5316-5323 Published: MAY 7 2003 |
| Times Cited: 118 References: 32 |
| Abstract: We recently reported the parallel synthesis of 140 degradable poly(beta-amino esters) via the conjugate addition of 20 primary or secondary amine monomers to seven different diacrylate monomers. To explore possible structure/function relationships and further characterize this class of materials, we investigated the ability of each DNA-complexing polymer to overcome important cellular barriers to gene transfer. The majority of vectors were found to be uptake-limited, but complexes formed from polymers B14 and G5 displayed high levels of internalization relative to "naked" DNA (18x and 32x, respectively). Effective diameter and zeta potential measurements indicated that, in general, small particle size and positive surface charge led to higher internalization rates. Of the 10 DNA/polymer complexes with the highest uptake levels, all had effective diameters less than 250 nm and nine had positive zeta potentials. Lysosomal trafficking was investigated by measuring the pH environment of delivered DNA. Complexes prepared with polymers G5, G10, A13, B13, A14, and B14 were found to have near neutral pH measurements, suggesting that they were able to successfully avoid trafficking to acidic lysosomes. This work highlights the value of parallel synthesis and screening approaches for the discovery of new polymers for gene delivery and the elucidation of structure/function relationships for this important class of materials. |
| Document Type: Article |
| Language: English |
| Reprint Address: Langer, R (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA |
Addresses:
1. MIT, Dept Chem Engn, Cambridge, MA 02139 USA
2. Univ Wisconsin, Dept Chem Engn, Madison, WI 53706 USA |
| Publisher: AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA |
| Subject Category: Chemistry, Multidisciplinary |
| IDS Number: 675FL |
| ISSN: 0002-7863 |
| DOI: 10.1021/ja034429c |
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