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PEG-Like Brush Polymer Conjugate of RNA Aptamer That Shows Reversible Anticoagulant Activity and Minimal Immune Response.

Publication ,  Journal Article
Ozer, I; Pitoc, GA; Layzer, JM; Moreno, A; Olson, LB; Layzer, KD; Hucknall, AM; Sullenger, BA; Chilkoti, A
Published in: Adv Mater
March 2022

Ribonucleic acid (RNA) therapeutics are an emerging class of drugs. RNA aptamers are of significant therapeutic and clinical interest because their activity can be easily reversed in vivo-a useful feature that is difficult to achieve using other therapeutic modalities. Despite their therapeutic promise, RNA aptamers are limited by their poor blood circulation. The attachment of polyethylene glycol (PEG) to RNA aptamers addresses this limitation. However, an RNA aptamer-PEG conjugate that is a reversible anticoagulant fails in a clinical trial due to the reactivity of the conjugate with pre-existing PEG antibodies and has cast a pall over PEGylation of aptamers and other biologics, despite its long history of utility in drug delivery. Here, PEG antibody-reactivity of this RNA aptamer is eliminated by conjugating it to a next-generation PEG-like brush polymer-poly[(oligoethylene glycol) methyl ether methacrylate)] (POEGMA). The conjugate retained the drug's therapeutic action and the ability to be easily reversed. Importantly, this conjugate does not bind pre-existing PEG antibodies that are prevalent in humans and does not induce a humoral immune response against the polymer itself in mice. These findings suggest a path to rescuing the PEGylation of RNA therapeutics and vaccines from the deleterious side-effects of PEG.

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Published In

Adv Mater

DOI

EISSN

1521-4095

Publication Date

March 2022

Volume

34

Issue

10

Start / End Page

e2107852

Location

Germany

Related Subject Headings

  • RNA
  • Polymers
  • Polyethylene Glycols
  • Nanoscience & Nanotechnology
  • Mice
  • Immunity
  • Aptamers, Nucleotide
  • Anticoagulants
  • Animals
  • 51 Physical sciences
 

Citation

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Chicago
ICMJE
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Ozer, I., Pitoc, G. A., Layzer, J. M., Moreno, A., Olson, L. B., Layzer, K. D., … Chilkoti, A. (2022). PEG-Like Brush Polymer Conjugate of RNA Aptamer That Shows Reversible Anticoagulant Activity and Minimal Immune Response. Adv Mater, 34(10), e2107852. https://doi.org/10.1002/adma.202107852
Ozer, Imran, George A. Pitoc, Juliana M. Layzer, Angelo Moreno, Lyra B. Olson, Kyle D. Layzer, Angus M. Hucknall, Bruce A. Sullenger, and Ashutosh Chilkoti. “PEG-Like Brush Polymer Conjugate of RNA Aptamer That Shows Reversible Anticoagulant Activity and Minimal Immune Response.Adv Mater 34, no. 10 (March 2022): e2107852. https://doi.org/10.1002/adma.202107852.
Ozer I, Pitoc GA, Layzer JM, Moreno A, Olson LB, Layzer KD, et al. PEG-Like Brush Polymer Conjugate of RNA Aptamer That Shows Reversible Anticoagulant Activity and Minimal Immune Response. Adv Mater. 2022 Mar;34(10):e2107852.
Ozer, Imran, et al. “PEG-Like Brush Polymer Conjugate of RNA Aptamer That Shows Reversible Anticoagulant Activity and Minimal Immune Response.Adv Mater, vol. 34, no. 10, Mar. 2022, p. e2107852. Pubmed, doi:10.1002/adma.202107852.
Ozer I, Pitoc GA, Layzer JM, Moreno A, Olson LB, Layzer KD, Hucknall AM, Sullenger BA, Chilkoti A. PEG-Like Brush Polymer Conjugate of RNA Aptamer That Shows Reversible Anticoagulant Activity and Minimal Immune Response. Adv Mater. 2022 Mar;34(10):e2107852.
Journal cover image

Published In

Adv Mater

DOI

EISSN

1521-4095

Publication Date

March 2022

Volume

34

Issue

10

Start / End Page

e2107852

Location

Germany

Related Subject Headings

  • RNA
  • Polymers
  • Polyethylene Glycols
  • Nanoscience & Nanotechnology
  • Mice
  • Immunity
  • Aptamers, Nucleotide
  • Anticoagulants
  • Animals
  • 51 Physical sciences