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
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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“Meanwhile, some compounds, such as chloroquine, imidazole, and zinc chloride, have also been combined with cationic vectors to further enhance endosomal escape [179–182].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [179]
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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
- Published
- 1996-03
- Volume
- 13
- Issue
- 3
- Pages
- 404-410
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- 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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