Pharmaceutical Prospects for RNA Interference

Schiffelers, Raymond M.; Woodle, Martin C.; Scaria, Puthupparampil V.

doi:10.1023/b:pham.0000012145.49054.6c

Cited by 73 publications

(40 citation statements)

References 48 publications

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“…There are five advantages of synthesized siRNAs: i) providing precise control of the amount and purity of siRNA used in the experiment; ii) siRNA can be characterized; iii) modifications can be introduced into the siRNA to enhance its target specificity; iv) high transfection efficiency into the cells of interest; and v) the initiation of siRNA-transfected silencing is immediate. (196,198) With the help of rapidly evolved siRNA synthetic chemistry and siRNA sequence design software, most current protocols for RNAi in mammalian systems use chemically synthesized siRNAs.…”

Section: A Mechanism Of Sirnamentioning

confidence: 99%

Gene Modulation for Treating Liver Fibrosis

Cheng

Mahato

2007

Crit Rev Ther Drug Carrier Syst

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Despite tremendous progress in our understanding of fibrogenesis, injury stimuli process, inflammation, and hepatic stellate cells (HSC) activation, there is still no standard treatment for liver fibrosis. Delivery of small molecular weight drug, proteins and nucleic acids to specific liver cell types remains a challenge due to the overexpression of extra cellular matrix (ECM) and consequent closure of sinusoidal gaps. In addition, activation of HSCs and subsequent release of inflammatory cytokines and infiltration of immune cells are other major obstacles to the treatment of liver fibrosis. To overcome these barriers, different therapeutic approaches are being investigated. Among them, modulation of certain aberrant protein production is quite promising for treating liver fibrosis. In this review, we will describe the mechanism of antisense, antigene and RNA interference (RNAi) therapies, and will discuss how the backbone modification of oligonucleotides affects their in vivo stability, biodistribution and bioactivity. Strategies for delivering these nucleic acids to specific cell types will be discussed. This review will critically address various insights developed in each individual strategy and for multipronged approaches, which will be helpful in achieving better outcomes.

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Section: A Mechanism Of Sirnamentioning

confidence: 99%

Gene Modulation for Treating Liver Fibrosis

Cheng

Mahato

2007

Crit Rev Ther Drug Carrier Syst

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“…The positive zeta-potential values indicate that the surface of the nanosystems is mostly composed of CS [26]. This net positive charge of the particle is desirable to promote electrostatic interaction with the ocular mucin [27]. In general, it was noted that zeta potential of the nanoparticles decreased as the CS/TPP ratio decreased.…”

Section: Particle Size and Zeta Potentialmentioning

confidence: 98%

Preparation and Characterization of Novel Drug-Inserted-Montmorillonite Chitosan Carriers for Ocular Drug Delivery

Hou¹,

Gui²,

Hu³

et al. 2015

ANP

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The objective of the study was to investigate the potential of montmorillonite as a sustained carrier in the preparation of drug-loaded nanoparticles for prolonged ocular application. Nanoparticles were prepared by ionic gelation of chitosan with sodium tripolyphosphate (TPP). Betaxolol hydrochloride (BH) was applied as a model drug. TG, FT-IR, TEM, DLS and XRD have been employed in the characterization of drug-encapsulated chitosan-montmorillonite/TPP nanoparticles (CS-MMT/TPP NPs). TEM images showed that the particles were spherical in shape and had a rough surface. The size range of the nanoparticles was between 338 and 585 nm with positive zeta potential values from 24 mV to 36 mV and encapsulation efficiency values ranging from 12.27% to 50.92%. In vitro sustained drug release was observed with the BH-loaded nanoparticles in artificial tears (pH 7.4). The results of FT-IR, TG and XRD showed that the drug was coated with CS-MMT/TPP NPs. In the mucoadhesion studies, an interaction was found between drug-loaded CS-MMT/TPP NPs and mucin, which could enhance precorneal residence time and hence facilitate an effective sustained release. The optimized formulation was determined to be non-irritant and tolerable by modified Draize test. Therefore, the BH-loading CS-MMT/TPP NPs developed are a promising carrier for controlled drug delivery to the eye.

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“…However, the mixed 21 -23 -nt siRNA duplexes may induce the off -target effect, and jeopardize the effectiveness and specifi city of gene silencing. Moreover, a thorough purifi cation is pivotal for this approach due to the possible interferon response induced by long dsRNAs in mammalian cells (Schiffelers et al, 2004 ). Nevertheless, an in vitro transcriptiondigestion technique is good for evaluation of the siRNA effect in a fast and inexpensive manner, but not for specifi c gene function analysis.…”

Section: Si Rna Designmentioning

confidence: 99%