Transdermal delivery of phosphorodiamidate Morpholino oligomers across hairless mouse skin

Pannier, Angela K.; Arora, Vikram; Iversen, Patrick L.; Brand, Rhonda M.

doi:10.1016/j.ijpharm.2004.02.001

Cited by 8 publications

(2 citation statements)

References 28 publications

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“…However, additional long-term studies are required to establish the level, extent and duration of the benefit and to design a treatment regimen that achieves sufficient dystrophin expression to prevent muscle loss and preserve muscle function. Systemic administration of AOs by a number of different routes, including intravenous, transdermal [36], subcutaneous and oral [37][38][39], has been reported.…”

Section: Discussionmentioning

confidence: 99%

Dystrophin expression in the mdx mouse after localised and systemic administration of a morpholino antisense oligonucleotide

Fletcher

Honeyman

Fall

et al. 2005

The Journal of Gene Medicine

164

128

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Section: Discussionmentioning

confidence: 99%

Dystrophin expression in the mdx mouse after localised and systemic administration of a morpholino antisense oligonucleotide

Fletcher

Honeyman

Fall

et al. 2005

The Journal of Gene Medicine

164

128

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“…Others have had less success in delivering antisense oligonucleotides into the skin, and this may be a function of the formulations that were used (Wraight and White, 2001). For example, we examined the influence of vehicle on the transdermal delivery of several PMO with different sizes, lengths, base compositions, sequences, and lipophilicities, and showed that the combination of sequence and formulation could modulate penetration through the skin (Pannier et al, 2004). We have also shown that some sequences can be more effective as topical agents because they interact with keratinocytes better than others (Brand et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Antisense Targeting of cFLIP Sensitizes Activated T Cells to Undergo Apoptosis and Desensitizes Responses to Contact Dermatitis

Mourich

Jendrzejewski

Marshall

et al. 2009

Journal of Investigative Dermatology

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Contact dermatitis is the result of inflammatory responses mediated by hapten-specific activated CD8+ and CD4+ T cells. Activation-induced cell death (AICD) is a naturally occurring process regulating the resolution of T-cell responses through decreased expression of the antiapoptotic molecule cellular FLICE inhibitory protein (cFLIP). We show that targeting cFLIP expression in vitro and in vivo, with morpholino antisense applied systemically or topically in conjunction with antigen, sensitizes T cells to undergo "early" AICD resulting in tolerance. Analysis of antisense-treated CD8+ OT-1 splenocytes after co-culture with SIINFEKL-pulsed DCs showed apoptosis occurring in a dose-dependent manner with respect to cFLIP peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) concentration. A transplant acceptance model using male DO.11 donor cells and female BALB/c recipient mice showed that cFLIP antisense treatment could promote antigen tolerance. Hypersensitivity responses induced in mice by the epicutaneous application of the haptens FITC and oxazolone confirmed that topically applied cFLIP antisense could reduce inflammation. Treatment of the skin produced significant reduction in dermatitis and localized infiltration of lymphocytes. Moreover, the treatment was target- and antigen-specific, dose-dependent, and capable of inducing long-lived tolerance. These data suggest that the targeted expression of immune-regulating molecules is possible through the application of antisense to the skin.

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Pharmacokinetics Of Nucleic‐Acid‐Based Therapeutics

Schmitz

Pandyra

Koropatnick

et al. 2010

Pharmaceutical Sciences Encyclopedia

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Nucleic‐acid‐based therapies consist of various forms of gene and antisense therapeutics. Gene and antisense therapeutics have unique applications based on local delivery, which limits the distribution of the therapeutic in the body and precludes considerations of their pharmacokinetics (PK). This article presents chemical structures of antisense oligonucleotides (ASOs) being developed as therapeutics and the published animal and human PK data regarding ASOs of two chemistries, exemplified by Genasense and OGX‐011.

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Transdermal delivery of phosphorodiamidate Morpholino oligomers across hairless mouse skin

Cited by 8 publications

References 28 publications

Dystrophin expression in the mdx mouse after localised and systemic administration of a morpholino antisense oligonucleotide

Dystrophin expression in the mdx mouse after localised and systemic administration of a morpholino antisense oligonucleotide

Antisense Targeting of cFLIP Sensitizes Activated T Cells to Undergo Apoptosis and Desensitizes Responses to Contact Dermatitis

Pharmacokinetics Of Nucleic‐Acid‐Based Therapeutics

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