Efficient tuning of siRNA dose response by combining mixed polymer nanocarriers with simple kinetic modeling.

ABSTRACT: Two of the most prominent challenges that limit the clinical success of siRNA therapies are a lack of control over cargo release from the delivery vehicle and an incomplete understanding of the link between gene silencing dynamics and siRNA dosing. Herein, we address these challenges through the formulation of siRNA polyplexes containing light-responsive polymer mixtures, whose varied compositions and triggered release behavior provide enhanced gene silencing and controlled dose responses that can be predicted by simple kinetic models. Through the straightforward mixing of two block copolymers, the level of gene knockdown was easily optimized to achieve the maximum level of GAPDH protein silencing in NIH/3T3 cells (~70%) using a single siRNA dose. The kinetic model was used to describe the

SUBMITTER: Greco CT 

PROVIDER: S-EPMC5317101 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature