Novel Polyaminolipids Enhance the Cellular Uptake of Oligonucleotides
| Autor: | Veeraiah Bodepudi, Judith K. Guy-Caffey, Jeffrey S. Bishop, Nilabh Chaudhary, Krishna Jayaraman |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Endosome
Molecular Sequence Data Oligonucleotides Spermine Biology Biochemistry chemistry.chemical_compound Tissue culture Chlorocebus aethiops Amphiphile Polyamines Animals Vero Cells Molecular Biology Base Sequence Oligonucleotide Phosphatidylethanolamines Cell Biology Lipids Quaternary Ammonium Compounds Spermidine Membrane chemistry Nucleic acid lipids (amino acids peptides and proteins) |
| Zdroj: | Journal of Biological Chemistry. 270:31391-31396 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.270.52.31391 |
| Popis: | Two new polyaminolipids have been synthesized for the purpose of improving cellular uptake of oligonucleotides. The amphipathic compounds are conjugates of spermidine or spermine linked through a carbamate bond to cholesterol. The polyaminolipids are relatively nontoxic to mammalian cells. In tissue culture assays, using fluorescent-tagged or radiolabeled triple helix-forming oligonucleotides, spermine-cholesterol and spermidine-cholesterol significantly enhance cellular uptake of the oligomers in the presence of serum. Spermine-cholesterol is comparable with DOTMA/DOPE (a 1:1 (w/w) formulation of the cationic lipid N-[1-(2,3-di oleyloxy)-propyl]-N,N,N-trimethylammonium chloride (DOTMA) and the neutral lipid dioleylphosphatidylethanolamine (DOPE)) in increasing cellular uptake of oligonucleotides, while spermidine-cholesterol is more efficient. The internalized oligonucleotides are routed to the nucleus as early as 20 min after treatment, suggesting that the polyaminolipids increase the permeability of cellular membranes to oligonucleotides. At later times, much of the incoming oligonucleotides are sequestered within punctate cytoplasmic granules, presumably compartments of endosomal origin. Coadministration with polyaminolipids markedly improves the cellular stability of the oligonucleotides; more than 80% of the material can be recovered intact up to 24 h after addition to cells. In the absence of the polyaminolipids, nearly all of the material is degraded within 6 h. These data suggest that the new polyaminolipids may be useful for the delivery of nucleic acid-based therapeutics into cells. |
| Databáze: | OpenAIRE |
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