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Cited by 80RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryDNA and Nucleic Acid Chemistry

The DOI matches its Crossref record; 30 of the 31 references it cites were found in a registry or an index.

Evaluation of Adjuvants that Enhance the Effectiveness of Antisense Oligodeoxynucleotides

Hughes, J. A., Aronsohn, A. I., Avrutskaya, A. V., Juliano, R. L.·1996·Pharmaceutical Research
DOI 10.1023/a:1016044609972
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Abstract

Purpose A factor limiting the effectiveness of antisense (AS) deoxyoligonucleotides (ODNs) is inefficient transport to their sites of action in the cytoplasm and in the nucleus. The extent of ODN transfer from endosomes to cytosol seems to be an important determinant of ODN effects. Consequently, the development of compounds (adjuvants) that enhance endosome to cytosol transfer may be vital in AS ODN therapeutics.Methods In this report, we evaluated compounds for their potential to enhance the effects of phosphorothioate ODNs. The test system used a CHO cell line expressing the enzyme chloramphenicol acetyl-transferase (CAT) under the control of an inducible promoter. Several potential endosomal disrupting adjuvants were screened, including: (a) fusogenic peptides; (b) a pH sensitive polymer; (c) polymeric dendrimers, (d) cationic liposomes and (e) a pH sensitive surfactant N-dodecyl 2-imidazole-propionate (DIP). ODN effects were evaluated at the protein level by quantitating levels of CAT.Results The use of AS ODN in co-incubation with the GALA peptide, cationic liposomes or 5th generation dendrimers resulted in a 35-40% reduction in CAT expression. The mis-matched ODN had no effect on CAT expression. Only modest effects were observed with the other adjuvants. DIP did not increase ODN activity by itself; however, when the liposomal form was used a significant reduction (48%) in CAT activity was seen.Conclusions We found the fusogenic peptide GALA, dendrimers, as well as the liposomal form of DIP, could significantly enhance the effects of ODNs.

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Crossref · 10.1023/a:1016044609972

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Research works printed but not linked: 1

  1. A. Martin. “Physical Pharmacy.” 1993 Lea & Febiger. Philadelphia.

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Metadata

Authors
Hughes, J. A., Aronsohn, A. I., Avrutskaya, A. V., & Juliano, R. L.
Affiliations
  • University of Florida (US)
  • University of North Carolina at Chapel Hill (US)
ORCID
Juliano, R. L.
Venue
Pharmaceutical Research
Publisher
Springer Science and Business Media LLC
Published
1996-03
Volume
13
Issue
3
Pages
404-410
ISSN
  • 0724-8741 (ISSN-L)
  • 1573-904X
DOI
10.1023/a:1016044609972
OpenAlex
W60020971
Cited by
80
References
31
Citations by year
2022: 1 · 2018: 1 · 2017: 1 · 2014: 4 · 2013: 3 · 2012: 2
FWCI
3.18
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Pharmaceutical Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
antisense oligodeoxynucleotides, adjuvants, endosomal escape, phosphorothioate oligonucleotides, GALA peptide, fusogenic peptides, dendrimers, cationic liposomes, pH-responsive polymers, chloramphenicol acetyltransferase reporter, gene delivery
MeSH terms
Adjuvants, Pharmaceutic, Amino Acid Sequence, Animals, Base Sequence, Drug Evaluation, Preclinical, Drug Synergism, Evaluation Studies as Topic, Cricetinae, Hydrogen-Ion Concentration, Imidazoles, Liposomes, Molecular Sequence Data, Surface-Active Agents, Transfection, Chloramphenicol O-Acetyltransferase, Oligonucleotides, Antisense, CHO Cells, Genes, Reporter

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.