Liposomal Delivery of Oligodeoxynucleotides

Tari, Ana M.; Khodadadian, Mojgan; Ellerson, Debra; Deisseroth, Albert; López-Berestein, Gabriel

doi:10.3109/10428199609067585

Cited by 24 publications

(7 citation statements)

References 19 publications

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“…We have previously demonstrated that neutral nanoliposomes are effective carriers for nucleotides in diverse animal models [117–120]. A DOPC loaded with antisense oligonucleotides against Grb2 is currently in advanced phase I clinical trial in leukemia [121], and no safety issues have been observed in this trial so far.…”

Section: Targeting Epha2 With Sirna-based Therapeuticsmentioning

confidence: 99%

Preclinical and clinical development of siRNA-based therapeutics

Özcan

Özpolat

Coleman

et al. 2015

Advanced Drug Delivery Reviews

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Discovery of RNA interference, first in plants and C. elegans and later in mammalian cells, led to the emergence of a transformative view in biomedical research. Knowledge of the multiple actions of non-coding RNAs has truly allowed viewing DNA, RNA and proteins in novel ways. Small interfering RNAs (siRNAs) can be used as tools to study single gene function both in vitro and in vivo and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of siRNAs in cancer therapy, many challenges remain, including rapid degradation, poor cellular uptake and off-target effects. Rational design strategies, selection algorithms, chemical modifications and nanocarriers offer significant opportunities to overcome these challenges. Here, we review the development of siRNAs as therapeutic agents from early design to clinical trial, with special emphasis on the development of EphA2-targeting siRNAs for ovarian cancer treatment.

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Section: Targeting Epha2 With Sirna-based Therapeuticsmentioning

confidence: 99%

Preclinical and clinical development of siRNA-based therapeutics

Özcan

Özpolat

Coleman

et al. 2015

Advanced Drug Delivery Reviews

Self Cite

401

301

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“…Encapsulation or incorporation in liposomes is currently the preferred method for the delivery of AS ODNs [21,29,32,41,45,[59][60][61][62][63][64][65][66][67][68][69] and, besides the intravenous infusion and subcutaneous, intramuscular or intraocular injection of naked ODNs, probably the only other method used in human clinical trials. (Ultimately, the suspensions of liposomes are also administered by infusion or injection.)…”

Section: Delivery Of As Odns: the Current Statusmentioning

confidence: 99%

The use of synthetic polymers for delivery of therapeutic antisense oligodeoxynucleotides

et al. 2002

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Developed over the past two decades, the antisense strategy has become a technology of recognised therapeutic potential, and many of the problems raised earlier in its application have been solved to varying extents. However, the adequate delivery of antisense oligodeoxynucleotides to individual cells remains an important and inordinately difficult challenge. Synthetic polymers appeared on this scene in the middle 1980s, and there is a surprisingly large variety used or proposed so far as agents for delivery of oligodeoxynucleotides. After discussing the principles of antisense strategy, certain aspects of the ingestion of macromolecules by cells, and the present situation of delivery procedures, this article analyses in detail the attempts to use synthetic polymers as carrier matrices and or cell membrane permeabilisation agents for delivery of antisense oligodeoxynucleotides. Structural aspects of various polymers, as well as the results, promises and limitations of their use are critically evaluated.

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“…9 Encapsulation of DNA into liposomes, however, has proved technically difficult, frequently resulting in entrapment efficiencies of <50%, 10 although there are a few exceptions. 9,11 To improve the incorporation of plasmid DNA, cationic lipids have been developed which, when incorporated into liposomes, can efficiently complex negatively charged DNA. Provided that the liposomes used also contain appropriate neutral lipids, such as dioleoylphosphatidylethanolamine (DOPE), the resulting complexes have been found to be effective for transfection in vitro [12][13][14][15][16] and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Plasmid DNA is Protected against Ultrasonic Cavitation-Induced Damage when Complexed to Cationic Liposomes

Wasan¹,

Reimer²,

Bally³

1996

Journal of Pharmaceutical Sciences

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Cationic liposomes bound to plasmid DNA are currently used for in vitro and in vivo gene therapy applications, but such complexes readily form large, heterogeneous aggregates that are not appropriate for pharmaceutical development. More importantly, size heterogeneity makes studies focused on optimizing gene transfer to cells difficult to conduct or understand. For this reason we have evaluated the effect of microprobe sonication on these complexes in an effort to achieve process-controlled size homogeneity. Complexes were prepared using a 7.2 kb reporter plasmid and the following liposomal lipid combinations: DDAB/DOPE (50:50 mol %), DDAB/DOPE/PEG-PE (50:45:5 mol %), DDAB/EPC (50:50 mol %), DDAB/EPC/PEG-PE (50:45:5, 50:40:10, 50:35:15 mol %), DODAC/DOPE (50:50 mol %), and DODAC/EPC (50:50 mol %) (DDAB, dimethyldioctadecylammonium bromide; DOPE, dioleoylphosphatidylethanolamine; PEG-PE, monomethoxypolyethylene glycol2000 succinate- distearoylphosphatidylethanolamine; EPC, egg phosphatidylcholine; DODAC, dioleoyldimethylammonium chloride). The influence of complex composition and lipid:DNA ratio was evaluated. Particle size was determined before and after complexation and again after sonication using the quasi-elastic light scattering technique. DNA integrity was assessed via agarose gel electrophoresis. Finally, gene transfection was evaluated using CHO cells that were transfected in vitro with sonicated and unsonicated complexes. It is established in this study that size reduction can occur, but this is dependent on cationic and neutral lipid composition and, in some cases, lipid:DNA ratio. Surprisingly, the process of sonication leaves a significant percentage of the plasmid DNA intact and capable of in vitro transfection. This study shows that plasmid DNA can be protected from damage due to sonication by liposome complex formation. This may indicate that more common pharmaceutical methods for size reduction which subject particles to mechanical stress may be applicable in preparation of liposome/DNA formulations for in vivo application.

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Liposomal Delivery of Oligodeoxynucleotides

Cited by 24 publications

References 19 publications

Preclinical and clinical development of siRNA-based therapeutics

Preclinical and clinical development of siRNA-based therapeutics

The use of synthetic polymers for delivery of therapeutic antisense oligodeoxynucleotides

Plasmid DNA is Protected against Ultrasonic Cavitation-Induced Damage when Complexed to Cationic Liposomes

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