Related Experiment Video
Updated: Jan 24, 2026

Predicting Gene Silencing Through the Spatiotemporal Control of siRNA Release from Photo-responsive Polymeric Nanocarriers
Published on: July 21, 2017
Pyruvate Responsiveness Based on α-Oxohydrazone Formation for Intracellular siRNA Release from Polyion Complex-Based
Hiroyasu Takemoto1, Chih-Ling Wang1, Takahiro Nomoto1
1Laboratory for Chemistry and Life Science, Institute of Innovative Research , Tokyo Institute of Technology , R1-11, 4259, Nagatsuta , Midori-Ku, Yokohama , Kanagawa 226-8503 , Japan.
Abstract:
Selective release of small interfering RNA (siRNA) payloads in response to intracellular substances is a prerequisite for the smart design of siRNA carriers. In this context, we developed a molecular program that allows reactivity with pyruvate for siRNA release in the cell on the basis of polyionic-complex- (PIC-) based siRNA carriers. Hydrazide can react with the α-keto acid structure of anionic pyruvate to form α-oxohydrazone, resulting in the reduction of the cationic net charge of the cationic polymer bearing a hydrazide moiety, which in turn leads to an inefficient electrostatic interaction with anionic siRNA and the consequent destabilization of the PIC (i.e., PGlu [DET/hydrazide]) in pyruvate-enriched environments, such as the cytoplasm, thus achieving effective siRNA release from the PIC and its associated gene-silencing activity. The present study provides the rationale for an α-oxohydrazone-formation-based smart design of pyruvate-responsive materials in the cell.
Related Concept Videos
Pyruvate Oxidation
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
Formation of Complex Ions
siRNA - Small Interfering RNAs
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
Factors Affecting α-Alkylation of Ketones: Choice of Base
The reaction involving bases like EtO− whose conjugate acid EtOH (pKa = 15.9) is stronger than the ketone (pKa = 19.2) results in an equilibrium mixture with higher ketone concentration. As a consequence,...
Base-Promoted α-Halogenation of Aldehydes and Ketones
Electron Carriers
Over the many stages of cellular respiration, glucose breaks down into carbon dioxide and water. Electron carriers pick up electrons lost by glucose in these reactions, temporarily storing and releasing them into the electron...

