Unlocking the potential of the human genome with RNA interference

  title={Unlocking the potential of the human genome with RNA interference},
  author={Gregory J. Hannon and John J. Rossi},
The discovery of RNA interference (RNAi) may well be one of the transforming events in biology in the past decade. RNAi can result in gene silencing or even in the expulsion of sequences from the genome. Harnessed as an experimental tool, RNAi has revolutionized approaches to decoding gene function. It also has the potential to be exploited therapeutically, and clinical trials to test this possibility are already being planned. 
The prospect of silencing disease using RNA interference.
The basic mechanism of RNAi and the therapeutic opportunities and obstacles for harnessing RNAi for therapy of human disease are discussed.
Tuning silence: conditional systems for RNA interference
The state of the art of systems allowing for drug-controllable knockdown, and a description of their current and future applications are summarized.
RNA interference in biology and disease.
This work has demonstrated success using RNAi to address the role of oncogene expression in leukemia cell lines and to validate the therapeutic potential of RNAi for treating these blood disorders.
Interference RNA for in vivo Knock-down of gene expression or genome-wide screening using shRNA.
Practical guidelines for RNAi working in rat are provided, based on the recent design and development of mice and rat Knock down models.
Strategies for silencing human disease using RNA interference
This work has highlighted both promise and challenges in using RNAi for therapeutic applications and suggests design and delivery strategies for RNAi effector molecules must be carefully considered to address safety concerns and to ensure effective, successful treatment of human diseases.
Genome-Wide RNA Interference: Functional Genomics in the Postgenomics Era.
The types of RNAi libraries available for understanding diverse biological questions are described and recent advances in RNAi screening methodologies in mouse, rat, humans, Drosophila, and worms are discussed.
On the delivery of small interfering RNAs into mammalian cells
  • M. Sioud
  • Biology
    Expert opinion on drug delivery
  • 2005
This review highlights recent advances in siRNA delivery, as well as challenging problems related to immune stimulation.
The best control for the specificity of RNAi.
RNA interference as potential therapy for neurodegenerative disease
The clearest application of RNAi to IBM is as a research tool to identify critical target genes that contribute to pathogenesis and provided that proximal pathogenic targets are identified, RNAi could surface as a potential therapeutic strategy to modulate their expression.


RNA interference: gene silencing in the fast lane.
Molecular medicine for the brain: silencing of disease genes with RNA interference
RNA interference : RNA
A conserved biological response to double-stranded RNA, known variously as RNA interference (RNAi) or post-transcriptional gene silencing, mediates resistance to both endogenous parasitic and
Small RNA: can RNA interference be exploited for therapy?
Expression profiling reveals off-target gene regulation by RNAi
RNA interference is thought to require near-identity between the small interfering RNA (siRNA) and its cognate mRNA. Here, we used gene expression profiling to characterize the specificity of gene
Free energy lights the path toward more effective RNAi
A pair of recent papers in Cell provides rules for designing short interfering RNAs (siRNAs) that are both validated at the practical level and understood mechanistically.
A large-scale RNAi screen in human cells identifies new components of the p53 pathway
The construction of a set of retroviral vectors encoding 23,742 distinct shRNAs, which target 7,914 different human genes for suppression, is reported, which confers resistance to both p53-dependent and p19ARF-dependent proliferation arrest, and abolishes a DNA-damage-induced G1 cell-cycle arrest.
A resource for large-scale RNA-interference-based screens in mammals
The construction and application of a shRNA expression library targeting 9,610 human and 5,563 mouse genes is reported, which suggests that the large-scale RNAi library can be used in specific, genetic applications in mammals, and will become a valuable resource for gene analysis and discovery.
Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells
The data suggest that siRNAs can induce nonspecific effects on protein levels that are siRNA sequence dependent but that these effects may be difficult to detect until genes central to a pivotal cellular response, such as p53 and p21, are studied.