Toxicity of cationic lipids and cationic polymers in gene delivery

Lv, Hongtao; Zhang, Shubiao; Wang, Bing; Cui, Shaohui; Yan, Jie

doi:10.1016/j.jconrel.2006.04.014

Cited by 1,966 publications

(1,531 citation statements)

References 100 publications

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“…Aside from the physical methods (in which siRNAs are directly injected into the cell cytoplasm or enter via membrane pores caused by electrical bursts), all the other methods share a common characteristic complexation with a positive (cationic) charge that enables the siRNAs to interact with the negatively charged plasma membrane. All of the commercial cationic lipids and polymers induce some cytotoxicity (reviewed in Lv et al 26 ) In addition, recent work also demonstrated that some cationic lipids can agonize Toll-like receptor 4 and induce interferons and proinflammatory cytokines. 27 On the contrary, cell-penetrating peptides and proteins are largely non-toxic and have the potential for specific targeting.…”

Section: Introductionmentioning

confidence: 99%

“…SNALPs encapsulating ApoB siRNAs significantly reduce ApoB mRNA levels in mice and non-human primates at reasonable doses (B2.5 mg kg À1 ). Although cationic lipids are known to cause toxicity, 26 the only reported adverse effects in animals are transient liver enzyme release. A Phase I clinical study that involved a single injection of ApoB siRNA-containing SNALPs showed target gene knockdown and serum cholesterol reduction and acceptable safety, although flu-like symptoms, indicative of stimulation of innate immune receptors, occurred at the highest dose.…”

Section: Introductionmentioning

confidence: 99%

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Special delivery: targeted therapy with small RNAs

2011

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Harnessing RNA interference using small RNA-based drugs has great potential to develop drugs designed to knock down expression of any disease-causing gene, thereby greatly expanding the universe of possible drug targets. However, delivering small RNAs into specific tissues and cells is still a hurdle. Here, we review recent progress in overcoming systemic, local and cellular barriers to RNA drug delivery, focusing on strategies for targeted uptake.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Special delivery: targeted therapy with small RNAs

2011

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“…Cette étude est la première, mais aussi la seule, à impliquer aussi directement une localisation nucléaire de TTF-1 comme marqueur de mauvais pronostic dans les cancers thyroïdiens bien différenciés. Zhang et al proposent qu'une altération de l'expression de TTF-1 soit impliquée dans les tumeurs thyroïdiennes [10] …”

Section: Ttf-1 Dans Les Cancers Du Poumonunclassified

TTF-1 : ni ange ni démon

Gilbert-Sirieix

Massaad-Massade

2011

Med Sci (Paris)

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“…While effective, these vectors have been limited by significant toxicity problems. 10 One strategy to enhance DNA vaccine potency is to deliver DNA into the highly immunogenic layers of the skin which harbours a wealth of antigen-presenting cells (APCs). 11 One of the predominant functions of the skin is the exclusion and detection of pathogens, 12 and the skin harbours a wealth of epidermal (known as Langherans cells [LCs]) and dermal dendritic cells (DCs) which serve as a link between the innate and adaptive branches of immunity.…”

Section: Introductionmentioning

confidence: 99%

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

Cole

McCaffrey

Ali

et al. 2016

Human Vaccines & Immunotherapeutics

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DNA vaccination holds the potential to treat or prevent nearly any immunogenic disease, including cancer. To date, these vaccines have demonstrated limited immunogenicity in vivo due to the absence of a suitable delivery system which can protect DNA from degradation and improve transfection efficiencies in vivo. Recently, microneedles have been described as a novel physical delivery technology to enhance DNA vaccine immunogenicity. Of these devices, dissolvable microneedles promise a safe, pain-free delivery system which may simultaneously improve DNA stability within a solid matrix and increase DNA delivery compared to solid arrays. However, to date little work has directly compared the suitability of different dissolvable matrices for formulation of DNA-loaded microneedles. Therefore, the current study examined the ability of 4 polymers to formulate mechanically robust, functional DNA loaded dissolvable microneedles. Additionally, complexation of DNA to a cationic delivery peptide, RALA, prior to incorporation into the dissolvable matrix was explored as a means to improve transfection efficacies following release from the polymer matrix. Our data demonstrates that DNA is degraded following incorporation into PVP, but not PVA matrices. The complexation of DNA to RALA prior to incorporation into polymers resulted in higher recovery from dissolvable matrices, and increased transfection efficiencies in vitro. Additionally, RALA/DNA nanoparticles released from dissolvable PVA matrices demonstrated up to 10-fold higher transfection efficiencies than the corresponding complexes released from PVP matrices, indicating that PVA is a superior polymer for this microneedle application.

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Toxicity of cationic lipids and cationic polymers in gene delivery

Cited by 1,966 publications

References 100 publications

Special delivery: targeted therapy with small RNAs

Special delivery: targeted therapy with small RNAs

TTF-1 : ni ange ni démon

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

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