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Small Silencing RNAs and Gene Therapy

  1. Dirk Grimm

Published Online: 17 JUN 2010

DOI: 10.1002/9780470015902.a0022396



How to Cite

Grimm, D. 2010. Small Silencing RNAs and Gene Therapy. eLS. .

Author Information

  1. University of Heidelberg, Department of Infectious Diseases, Virology, Cluster of Excellence CellNetworks, Bioquant, Heidelberg, Germany

Publication History

  1. Published Online: 17 JUN 2010


Within one decade, ribonucleic acid interference (RNAi), that is, the sequence-specific knockdown of gene expression triggered by small silencing RNAs, has rapidly matured from a biological curiosity into our single most promising biotherapeutic for a wide array of human diseases. Its exciting looming clinical translation is particularly accelerated by the increasingly pursued juxtaposition of RNAi technologies with established gene therapy methodologies. Fostering this mutual attraction of two potent clinical modalities and paving the way to fully harness their therapeutic power are the abilities of viral gene transfer vectors to mediate stable, efficient and tailored transduction of RNAi into recipient cells. Finally, moreover adding to the enormous promise of combining small silencing RNAs and gene therapy are latest findings on the role of endogenous microRNAs for various human diseases, further enlarging our already fertile chest of tools and targets for intervention and fortifying the optimism that RNAi gene therapies will soon become a clinical reality.

Key Concepts:

  • Expression of RNAi triggers from viral gene transfer vehicles is a potent strategy to optimise the issues of in vivo delivery and specificity.

  • Vice versa, the development of expressible, vector-compatible RNAi triggers adds a crucial therapeutically relevant template to our arsenal of gene therapy vectors.

  • The combination of RNAi and gene therapy thus synergistically enhances the power and promise of each individual approach.

  • Beyond exploiting RNAi to directly target and destroy disease-associated genes, cellular miRNAs can also be used to segregate vectors or viruses.

  • This allows to either direct transgene expression to a certain subset of cells in the body, or to increase the specificity and safety of oncolytic viruses.

  • Further improvements of RNAi gene therapy vectors concern the promoter, which can be constitutive or inducible, weak or strong, or specific or ubiquitous.

  • Concurrent advances in viral vector genome designs and structures help to maintain a threshold of RNAi expression required for potent gene silencing.

  • Latest improvements in the field of RNAi gene therapy vectors comprise combinatorial approaches either aiming at enhancing custom vector properties or juxtaposing various RNAi triggers and other gene silencers, or co-targeting different viral or cellular genes, to avert target viral escape by mutation.


  • RNA interference;
  • RNAi;
  • small silencing RNAs;
  • short hairpin RNA;
  • microRNA;
  • gene therapy;
  • AAV vectors;
  • posttranscriptional regulation;
  • molecular evolution;
  • combinatorial RNAi