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Cited by 808

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In Vitro Gene Delivery by Degraded Polyamidoamine Dendrimers

Tang, Mary X., Redemann, Carl T., Szoka, Francis C.·1996·Bioconjugate Chemistry
DOI 10.1021/bc9600630
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Abstract

Transfection of cultured cells has been reported using complexes between DNA and spherical cationic polyamidoamine polymers (Starburst dendrimers) that consist of primary amines on the surface and tertiary amines in the interior. The transfection activity of the dendrimers is dramatically enhanced (> 50-fold) by heat treatment in a variety of solvolytic solvents, e.g., water or butanol. Such treatment induces significant degradation of the dendrimer at the amide linkage, resulting in a heterodisperse population of compounds with molecular weights ranging from the very low (< 1500 Da) to several tens of kilodaltons. The compound facilitating transfection is the high molecular weight component of the degraded product and is denoted as a "fractured" dendrimer. Transfection activity is related both to the initial size of the dendrimer and its degree of degradation. Fractured dendrimers exhibit an increased apparent volume change as measured by an increase in the reduced viscosity upon protonation of the terminal amines as pH is reduced from 10.5 to 7.2 whereas intact dendrimers do not. Dendrimers with defective branching have been synthesized and also have improved transfection activity compared to that of the intact dendrimers. For a series of heat-treated dendrimers we observe a correlation between transfection activity and the degree of flexibility, computed with a random cleavage simulation of the degradation process. We suggest that the increased transfection after the heating process is principally due to the increase in flexibility that enables the fractured dendrimer to be compact when complexed with DNA and swell when released from DNA.

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Authors
Tang, M. X., Redemann, C. T., & Szoka, F. C.
Venue
Bioconjugate Chemistry
Publisher
American Chemical Society (ACS)
Published
1996-01-01
Volume
7
Issue
6
Pages
703-714
ISSN
  • 1043-1802 (ISSN-L)
  • 1520-4812
DOI
10.1021/bc9600630
OpenAlex
W2043764483
Cited by
808
References
0
FWCI
27.27
Type
journal article
Language
en
Open access
closed

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