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Mixed-surface polyamidoamine polymer variants retain nucleic acid-scavenger ability with reduced toxicity.

Publication ,  Journal Article
Olson, LB; Hunter, NI; Rempel, RE; Yu, H; Spencer, DM; Sullenger, CZ; Greene, WS; Varanko, AK; Eghtesadi, SA; Chilkoti, A; Pisetsky, DS ...
Published in: iScience
December 22, 2022

Nucleic acid-binding polymers can have anti-inflammatory properties and beneficial effects in animal models of infection, trauma, cancer, and autoimmunity. PAMAM G3, a polyamidoamine dendrimer, is fully cationic bearing 32 protonable surface amines. However, while PAMAM G3 treatment leads to improved outcomes for mice infected with influenza, at risk of cancer metastasis, or genetically prone to lupus, its administration can lead to serosal inflammation and elevation of biomarkers of liver and kidney damage. Variants with reduced density of cationic charge through the interspersal of hydroxyl groups were evaluated as potentially better-tolerated alternatives. Notably, the variant PAMAM G3 50:50, similar in size as PAMAM G3 but with half the charge, was not toxic in cell culture, less associated with weight loss or serosal inflammation after parenteral administration, and remained effective in reducing glomerulonephritis in lupus-prone mice. Identification of such modified scavengers should facilitate their development as safe and effective anti-inflammatory agents.

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Published In

iScience

DOI

EISSN

2589-0042

Publication Date

December 22, 2022

Volume

25

Issue

12

Start / End Page

105542

Location

United States
 

Citation

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Chicago
ICMJE
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Olson, L. B., Hunter, N. I., Rempel, R. E., Yu, H., Spencer, D. M., Sullenger, C. Z., … Sullenger, B. A. (2022). Mixed-surface polyamidoamine polymer variants retain nucleic acid-scavenger ability with reduced toxicity. IScience, 25(12), 105542. https://doi.org/10.1016/j.isci.2022.105542
Olson, Lyra B., Nicole I. Hunter, Rachel E. Rempel, Haixiang Yu, Diane M. Spencer, Cynthia Z. Sullenger, William S. Greene, et al. “Mixed-surface polyamidoamine polymer variants retain nucleic acid-scavenger ability with reduced toxicity.IScience 25, no. 12 (December 22, 2022): 105542. https://doi.org/10.1016/j.isci.2022.105542.
Olson LB, Hunter NI, Rempel RE, Yu H, Spencer DM, Sullenger CZ, et al. Mixed-surface polyamidoamine polymer variants retain nucleic acid-scavenger ability with reduced toxicity. iScience. 2022 Dec 22;25(12):105542.
Olson, Lyra B., et al. “Mixed-surface polyamidoamine polymer variants retain nucleic acid-scavenger ability with reduced toxicity.IScience, vol. 25, no. 12, Dec. 2022, p. 105542. Pubmed, doi:10.1016/j.isci.2022.105542.
Olson LB, Hunter NI, Rempel RE, Yu H, Spencer DM, Sullenger CZ, Greene WS, Varanko AK, Eghtesadi SA, Chilkoti A, Pisetsky DS, Everitt JI, Sullenger BA. Mixed-surface polyamidoamine polymer variants retain nucleic acid-scavenger ability with reduced toxicity. iScience. 2022 Dec 22;25(12):105542.
Journal cover image

Published In

iScience

DOI

EISSN

2589-0042

Publication Date

December 22, 2022

Volume

25

Issue

12

Start / End Page

105542

Location

United States