Intestinal delivery of non-viral gene therapeutics: physiological barriers and preclinical models

O’Neill, Martin J.; Bourré, Ludovic; Melgar, Silvia; O’Driscoll, Caitriona M.

doi:10.1016/j.drudis.2011.01.003

Cited by 111 publications

(86 citation statements)

References 158 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Oral delivery might constitute an excellent treatment strategy that could offer convenient and patient-friendly features; however, progress in this approach has been hampered by substantial challenges associated with biological barriers that limit the oral activity of nucleic acid therapeutics. 12 In this context, we used a pertinent transgenic mouse model over-expressing the microRNA miR-30b in the mammary gland 13 in order to study the horizontal delivery of microRNAs via the oral ingestion of miR-30b-enriched milk by the pups. Sensitive, mature microRNA-specific RT-qPCR assays were used to quantify miR-30b variations in the blood, small intestine, liver, lung and kidney of pups fed by transgenic or non-transgenic females.…”

Section: Introductionmentioning

confidence: 99%

No effect of an elevated miR-30b level in mouse milk on its level in pup tissues

et al. 2015

View full text Add to dashboard Cite

(2015) No effect of an elevated miR-30b level in mouse milk on its level in pup tissues, RNA Biology, 12:1, 26-29, DOI: 10.1080/15476286.2015 Keywords: diet, horizontal genetic transfer, microRNA, milk, transgenic mouseRecent reports have shown that ingested microRNAs may be transferred to blood, accumulate in tissues and exert canonical regulation on endogenous transcripts. In spite of several attempts to replicate these findings, they have not been confirmed and several questions remain. By using a transgenic mouse model presenting a high level of miR-30b in milk, the horizontal delivery of this microRNA via oral ingestion was studied in pups. Our findings demonstrated that, although very high levels of miR-30b were found in milk and in stomach contents of the pups, we did not detect an increase in miR-30b in tissues of pups fed by transgenic females compared to pups fed by wild-type females.

show abstract

Section: Introductionmentioning

confidence: 99%

No effect of an elevated miR-30b level in mouse milk on its level in pup tissues

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Local expression of therapeutic proteins may have therapeutic benefit in the treatment of inflammatory bowel disease, intestinal cancer, and the intestinal symptoms of cystic fibrosis (O' Neill et al 2011) (Page and Cudmore 2001). Furthermore, the intestine can potentially provide a route of entry into the bloodstream for locally expressed therapeutic proteins such as Factor VIII in haemophilia patients (Bowman et al 2008), or indeed for gene therapies to distant disease sites.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic studies on the uptake and intracellular trafficking of novel cyclodextrin transfection complexes by intestinal epithelial cells

Neill

Guo

Byrne

et al. 2011

International Journal of Pharmaceutics

View full text Add to dashboard Cite

“…This safe consumption results in part from extensive barriers to ingested RNAs, such as low gut pH, nucleases, multiple membrane barriers, and rapid renal elimination of RNA . These barriers are also evidenced by drug delivery challenges faced by developers of oligonucleotide-based drugs (Juliano et al 2009;O'Neill et al 2011;Petrick et al 2013). Further studies in mammals indicate that ingested doublestranded RNAs, even those targeting a gene in the test species, do not produce adverse health effects in these animals (Petrick et al 2015).…”

Section: Jan Verhaert and Jay S Petrick Monsanto Company Belgium Amentioning

confidence: 99%

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop

Aigner¹,

Buesen²,

Gant³

et al. 2016

Regulatory Toxicology and Pharmacology

View full text Add to dashboard Cite

The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that the abundance of data obtained from ncRNA expression profiling requires careful evaluation to determine the utility of specific ncRNAs for regulatory toxicology. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify candidate ncRNAs for further assessment as potential biomarkers of toxicity and areas of toxicology where ncRNA expression profiling can address prevailing scientific deficiencies.(2) Develop consensus on how to conduct and report ncRNA expression profiling in a toxicological context to support applicability for regulatory decision-making. (3) Conduct experimental projects to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. As necessary, retrospective analyses (e.g. from surplus samples from control groups from regulatory studies) can be supplemented with new (90-day) rat oral toxicity studies. These projects should aim at establishing physiological ncRNA expression profiles including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be linked with substance-induced apical effects in a dose-dependent manner. Applying a holistic approach, knowledge on ncRNAs, and relevant information from 'omics and epigenetics technologies, should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context.

show abstract

Intestinal delivery of non-viral gene therapeutics: physiological barriers and preclinical models

Cited by 111 publications

References 158 publications

No effect of an elevated miR-30b level in mouse milk on its level in pup tissues

No effect of an elevated miR-30b level in mouse milk on its level in pup tissues

Mechanistic studies on the uptake and intracellular trafficking of novel cyclodextrin transfection complexes by intestinal epithelial cells

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop

Contact Info

Product

Resources

About