RNAi and small interfering RNAs in human disease therapeutic applications

Lares, Monica; Rossi, John J.; Ouellet, Dominique L.

doi:10.1016/j.tibtech.2010.07.009

Cited by 254 publications

(185 citation statements)

References 77 publications

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“…One is focused on understanding of the mechanisms of siRNA in order to improve its design as a potent therapeutic agent for particular disease and the other is to address how to deliver well-designed drug candidate siRNA into target cells or tissues specifically as well as efficiently, and this is particularly pertinent in cancer therapy. In most studies up to now, efforts have been made separately to improve either specific targeting or efficiency of intracellular delivery, reviewed by Lares MR. 26 Antibody-directed delivery was first experimented to guide anti-cancer drugs and used for specific delivery of siRNA as well. 27,28 In recent years, nucleic acid aptamers have showed new promise as specific ligands for diagnostic or therapeutic use.…”

Section: Discussionmentioning

confidence: 99%

A specific aptamer-cell penetrating peptides complex delivered siRNA efficiently and suppressed prostate tumor growthin vivo

Yanjun

Liu

et al. 2016

Cancer Biology & Therapy

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Specific and efficient delivery of siRNA into intended tumor cells remains as a challenge, even though RNAi has been exploited as a new strategy for prostate cancer therapy. This work aims to address both specificity and efficiency of SURVIVIN-siRNA delivery by constructing a therapeutic complex using combinatorial strategies. A fusion protein STD was first expressed to serve as a backbone, consisting of streptavidin, a cell-penetrating peptide called Trans-Activator of Transcription (TAT) and a doublestranded RNA binding domain. A biotinylated Prostate Specific Membrane Antigen (PSMA) specific aptamer A10 and SURVIVIN-siRNA were then linked to STD protein to form the therapeutic complex. This complex could specifically targeted PSMA C tumor cells. Compared to lipofectamine and A10-siRNA chimera, it demonstrated higher efficiency in delivering siRNA into target cells by 19.2% and 59.9%, and increased apoptosis by 16.8% and 26.1% respectively. Upon systemic administration, this complex also showed significant efficacy in suppressing tumor growth in athymic mice (p <0.001). We conclude that this therapeutic complex could specifically and efficiently deliver SURVIVIN-siRNA to target cells and suppressed tumor growth in vivo, which indicates its potential to be used as a new strategy in prostate cancer therapy

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Section: Discussionmentioning

confidence: 99%

A specific aptamer-cell penetrating peptides complex delivered siRNA efficiently and suppressed prostate tumor growthin vivo

Yanjun

Liu

et al. 2016

Cancer Biology & Therapy

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“…I de siste årene har polymerer vist seg å vaere egnet for målstyring av peptider, antistoffer og genmateriale (13). I tillegg til målstyring, beskytter polymerene disse substansene mot enzymatisk degradering etter intravenøs injeksjon (14). Flere typer polymere nanopartikler gjennomgår per dags dato kliniske studier (15).…”

Section: Klinisk Anvendelseunclassified

Nanomedisin i kreftbehandling – håp til små partikler

Evjen¹

2015

Tidsskriftet

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“…38 They have the advantages of delivering siRNAs to nondividing cells and of improving biosafety by diminishing submit your manuscript | www.dovepress.com…”

Section: Viral Delivery Systemsmentioning

confidence: 99%

“…38 This method can decrease immunogenicity and is much safer. 64 Well designed lipid delivery systems can bypass the endosome and release siRNA.…”

Section: Liposome Delivery Systemsmentioning

confidence: 99%

Progress on RNAi-based molecular medicines

Chen¹,

Xie²

2012

IJN

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RNA interference (RNAi) is a promising strategy to suppress the expression of disease-relevant genes and induce post-transcriptional gene silencing. Their simplicity and stability endow RNAi with great advantages in molecular medicine. Several RNAi-based drugs are in various stages of clinical investigation. This review summarizes the ongoing research endeavors on RNAi in molecular medicine, delivery systems for RNAi-based drugs, and a compendium of RNAi drugs in different stages of clinical development. Of special interest are RNAi-based drug target discovery and validation, delivery systems for RNAi-based drugs, such as nanoparticles, rabies virus protein-based vehicles, and bacteriophages for RNA packaging. Keywords: RNA interference, delivery systems, liposome, nanoparticle, molecular medicines Overview of RNA interferenceRNA plays key roles in organisms beyond the traditional role of being a messenger bridging genetic information and biosynthesis of protein. Endogenous or exogenous double-stranded RNA can be cleaved into 21-23-nucleotide small interfering RNA (siRNA) by the endonuclease, Dicer. siRNA can unzip into a guide strand and a passenger strand. The latter will be subsequently degraded. The guide strand is then incorporated into the RNA-induced silencing complex and binds to the target mRNA, inducing mRNA degradation by Argonaute, a component of the RNA-induced silencing complex which affects protein synthesis (Figure 1). This phenomenon is known as RNA interference (RNAi) 1-4 and is well established in diverse organisms. There are three major types of small RNA used to silence gene function by RNAi technology, ie, microRNA (miRNA), siRNA, and short hairpin RNAs (shRNA). 5,6 Although all small RNAs are 22-24 nucleotides in length, [7][8][9] there are some important differences between them. First, siRNA, processed from exogenously introduced strictly base-paired siRNA duplexes, are completely complementary to their target mRNA and facilitate cleavage of bases 10-12 at the 5′ end of the guide strand, 10,11 resulting in transient silence of the target gene. Second, shRNA, inserting in a Pol III expression cassette, can be transfected or packaged into a recombinant virus and introduced into target cells. 5 The advantage of shRNA is prolonged expression of the RNAi effect. Third, miRNA or chimeric miRNA/shRNA, derived from endogenously encoded shRNAs, 5 can mediate gene silencing post-transcriptionally, and bind partially to complementary miRNA target sequences located in the 3′ untranslated regions of target mRNAs, 9 but the "seed" region located in bases 2-8 is highly complementary. 12 The seed region can RNAi as a tool for discovery of drug targetsMost drugs function via blocking of their targets. The simplicity and stability of RNAi in gene silencing make it a powerful tool in drug research and development.16 RNAi-based drug target discovery includes the following steps. Identification of target genesThe selection of target gene is crucial and, to great extent, determines whether subse...

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RNAi and small interfering RNAs in human disease therapeutic applications

Cited by 254 publications

References 77 publications

A specific aptamer-cell penetrating peptides complex delivered siRNA efficiently and suppressed prostate tumor growthin vivo

A specific aptamer-cell penetrating peptides complex delivered siRNA efficiently and suppressed prostate tumor growthin vivo

Nanomedisin i kreftbehandling – håp til små partikler

Progress on RNAi-based molecular medicines

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