RNA-interference-based Gene Therapy Approaches to HIV Type-1 Treatment: Tackling the Hurdles from Bench to Bedside

Eije, Karin J. von; Berkhout, Ben

doi:10.1177/095632020901900602

Cited by 9 publications

(7 citation statements)

References 150 publications

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“…RNA interference (RNAi) is a physiological process that results in sequence-specific gene silencing by cleavage of the targeted messenger RNA and can be used to knock down therapeutic targets in cancer cells such as elements of pro-oncogenic signaling pathways [17,23,25]. Lentiviruses are considered to be efficient for transferring siRNA and are currently being tested in clinical trials [26][27][28]. Once A549 cells were exposed to the anti-RalA virus and compared with a negative control virus (containing a scrambled siRNA sequence), the expression level of RalA was evaluated up to day 6 post-infection and found to be markedly reduced at each time point (Fig.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of RalA signaling pathway in treatment of non-small cell lung cancer

et al. 2012

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Section: Resultsmentioning

confidence: 99%

Inhibition of RalA signaling pathway in treatment of non-small cell lung cancer

et al. 2012

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“…For instance, antiviral gene therapy based on the mechanism of RNA interference (RNAi) uses short hairpin RNA (shRNA) inhibitors that target the viral RNA genome 8 , 9 . We previously demonstrated that RNAi attack is influenced by the local RNA structure of the HIV-1 RNA target sequence 10 , 11 and more recently reported that the design of shRNA inhibitors can be significantly improved by the exclusive targeting of accessible HIV-1 RNA domains as determined by SHAPE technology 12 …”

Section: Introductionmentioning

confidence: 99%

On the role of four small hairpins in the HIV-1 RNA genome

Knoepfel

Berkhout

2013

RNA Biology

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An RNA secondary structure model for the complete HIV-1 genome has recently been published based on SHAPE technology. Several well-known RNA motifs such as TAR and RRE were confirmed and numerous new structured motifs were described that may play important roles in virus replication. The 9 kb viral RNA genome is densely packed with many RNA hairpin motifs and the collective fold may play an important role in HIV-1 biology. We initially focused on 16 RNA hairpin motifs scattered along the viral genome. We considered conservation of these structures, despite sequence variation among virus isolates, as a first indication for a significant function. Four relatively small hairpins exhibited considerable structural conservation and were selected for experimental validation in virus replication assays. Mutations were introduced into the HIV-1 RNA genome to destabilize individual RNA structures without affecting the protein-coding properties (silent codon changes). No major virus replication defects were scored, suggesting that these four hairpin structures do not play essential roles in HIV-1 replication.

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“…Several recent reviews have been written on the subject [45,63,64]. The delivery of nucleic acid based drugs is characterized by a number of common challenges.…”

Section: Sirna Delivery -Challenges Of Deliverymentioning

confidence: 99%

Recent Patents in Antiviral siRNAs

Saravolac

Wong²,

Cairns³

2010

PRI

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The advent of gene silencing siRNA technology has created opportunities to develop therapeutics based on targeting the genomics of the disease state. Amongst the first applications of siRNA technology, antiviral applications have been quickly and extensively exploited allowing emergence of a range of antiviral therapeutic strategies. Patent activity has encompassed a range of the components required to utilize this technology ranging from the identification of susceptible genomic targets through to the development of vector systems to express the siRNA endogenously or the synthesis of stable RNA oligonucleotides for in vivo therapeutics. Indeed the primary focus of research effort in this area has been to overcome the challenge common to all of gene therapeutics - delivery of the oligonucleotide - to the diseased tissues and organs, sites of infection and/or sites of drug action. Here we survey the development of siRNA therapeutics both in terms of the range of virus species targeted and the strategic approaches employed. Our study illustrates features commonly observed in the field of nucleic acid drug development. While in vitro studies provide a broad range of molecules and molecular targets for potential therapeutics, the field is however severely limited in terms of safe, effective means to deliver the potential siRNA therapeutics in vivo, to the intracellular site of action.

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RNA-interference-based Gene Therapy Approaches to HIV Type-1 Treatment: Tackling the Hurdles from Bench to Bedside

Cited by 9 publications

References 150 publications

Inhibition of RalA signaling pathway in treatment of non-small cell lung cancer

Inhibition of RalA signaling pathway in treatment of non-small cell lung cancer

On the role of four small hairpins in the HIV-1 RNA genome

Recent Patents in Antiviral siRNAs

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