Technology ID

Inducible Activation Nucleic Acid Hybrid Switch for Conditional Generation of Oligonucleotides

Lead Inventor
Shapiro, Bruce (NCI)
Zakrevsky, Paul (NCI)
Therapeutic Areas
Development Stages
Pre-clinical (in vivo)
Lead IC

Gene therapy research has yielded FDA-approved treatments for an array of diseases. However, challenges facing nucleic-acid based therapeutics include non-specific delivery and degradation of the nanoparticles. NCI investigators have developed a solution to address these challenges in their novel nucleic-based therapy based on the conditional activation strategy. 

The inducible activation nucleic acid hybrid switch overcomes the drawbacks of current technologies through its unique design. The implementation of nucleic acid logic elements in these constructs circumvents off-target effects. The functional oligonucleotide constructs would only be generated and activated in environments denoted by the presence or absence of a specific cognate RNA trigger, ensuring context-sensitive function. The systems were also optimized to be resistant to nuclease degradation yet inexpensive for commercial production. Furthermore, this collection of logic-based systems can accommodate different trigger/target sequence pairs, enhancing its diversity of application, and serves as a novel paradigm for conditionally regulated therapeutics against cancer, genetic disorders, or infectious diseases. The NCI is looking for innovative companies interested in co-developing and/or licensing this technology.

Competitive Advantages:

  • Resistant to nuclease degradation
  • Specificity of action based on environmental context, minimizing off-target effects
  • Amenable to alterations to accommodate different trigger/target sequence pairs without the need for sequence overlap or similarities 
  • A set of context sensitive drugs that separate diagnosis (disease state – e.g. over or under expression of particular genes) from the therapeutic state (targeting specific genes – e.g. Dicer substrate RNAs that induce apoptosis)

Commercial Applications:

  • Cancer
  • Infectious diseases
  • Genetic disorders 
Licensing Contact: