Cyclodextrin gene vectors: cell trafficking and the influence of lipophilic chain length

Mcmahon, Anthony; Gomez, E.; Donohue, Ruth; Forde, Damien; Darcy, Raphael; O’Driscoll, Caitriona M.

doi:10.1016/s1773-2247(08)50060-8

Cited by 33 publications

(42 citation statements)

References 28 publications

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“…1 (b, d)). This type of positioning is similar to that of the majority of CD-based gene delivery vectors investigated by our group (Cryan et al, 2004a;McMahon et al, 2008;McMahon et al, 2012).…”

Section: Introductionsupporting

confidence: 73%

“…This may also have implications for transfection. For example, greater gene expression was mediated by CDs whose lipophilic group consisted of longer rather than shorter hydrocarbon chains (Cryan et al, 2004a;McMahon et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…CD complexes were prepared as previously described (Cryan et al, 2004a;McMahon et al, 2008;O' Neill et al, 2011). Briefly, CDs were weighed and dissolved in chloroform to give a 1 mg/ml solution.…”

Section: Preparation Of Vectorsirna Complexesmentioning

confidence: 99%

“…In addition, CDs lend themselves to chemical modifications at the primary and/or secondary faces yielding a series of compounds with diverse properties, which render them useful for gene delivery. In particular, cationic and amphiphilic CDs have shown low toxicity and high transfection efficiency in various cell types (Cryan et al, 2004a;McMahon et al, 2008;Méndez-Ardoy et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Characterisation of cationic amphiphilic cyclodextrins for neuronal delivery of siRNA: Effect of reversing primary and secondary face modifications

O’Mahony

Doyle

Darcy

et al. 2012

European Journal of Pharmaceutical Sciences

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Section: Introductionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Preparation Of Vectorsirna Complexesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterisation of cationic amphiphilic cyclodextrins for neuronal delivery of siRNA: Effect of reversing primary and secondary face modifications

O’Mahony

Doyle

Darcy

et al. 2012

European Journal of Pharmaceutical Sciences

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“…This "mixing method" for CD.siRNA complex preparation was previously optimized for CD.DNA complexes. 17,22,24 Preparation of Lf2000.siRNA Complexes. Lipofectamine 2000 (Invitrogen) (Lf2000) is a cationic lipid-based transfection reagent.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Click-Modified Cyclodextrins as Nonviral Vectors for Neuronal siRNA Delivery

O’Mahony

Godinho

Ogier

et al. 2012

ACS Chem. Neurosci.

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RNA interference (RNAi) holds great promise as a strategy to further our understanding of gene function in the central nervous system (CNS) and as a therapeutic approach for neurological and neurodegenerative diseases. However, the potential for its use is hampered by the lack of siRNA delivery vectors which are both safe and highly efficient. Cyclodextrins have been shown to be efficient and low toxicity gene delivery vectors in various cell types in vitro. However, to date, they have not been exploited for delivery of oligonucleotides to neurons. To this end, a modified β-cyclodextrin (CD) vector was synthesized, which complexed siRNA to form cationic nanoparticles of less than 200 nm in size. Furthermore, it conferred stability in serum to the siRNA cargo. The in vitro performance of the CD in both immortalized hypothalamic neurons and primary hippocampal neurons was evaluated. The CD facilitated high levels of intracellular delivery of labeled siRNA, while maintaining at least 80% cell viability. Significant gene knockdown was achieved, with a reduction in luciferase expression of up to 68% and a reduction in endogenous glyceraldehyde phosphate dehydrogenase (GAPDH) expression of up to 40%. To our knowledge, this is the first time that a modified CD has been used as a safe and efficacious vector for siRNA delivery into neuronal cells.

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Gene Delivery with Cyclodextrins

Wintgens

2011

Cyclodextrins in Pharmaceutics, Cosmetics, and Biomedicine

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Cyclodextrin gene vectors: cell trafficking and the influence of lipophilic chain length

Cited by 33 publications

References 28 publications

Characterisation of cationic amphiphilic cyclodextrins for neuronal delivery of siRNA: Effect of reversing primary and secondary face modifications

Characterisation of cationic amphiphilic cyclodextrins for neuronal delivery of siRNA: Effect of reversing primary and secondary face modifications

Click-Modified Cyclodextrins as Nonviral Vectors for Neuronal siRNA Delivery

Gene Delivery with Cyclodextrins

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