Jens G. Hjörleifsson, MS from Stockholm University presents the above titled seminar.
Deoxyribozymes or Dz's (Dz's), are catalytically active short single-stranded DNA sequences capable of cleaving mRNA at purine/pyrimidine junctions with high specificity, making them a good candidate for gene silencing purposes. A potent Dz the 10-23 Dz has not been successfully used in vivo due to its low stability in body fluids and poor cellular delivery past the plasma membrane. With chemical modifications and better delivery methods the goal of measuring positive biological response in animal models and human patients is not far away.
Chemical modifications however, come at a price, where activity is generally lowered, toxicity higher and synthesis and purification is more costly for the most commonly used modifications. Non-toxic, short hairpins and other secondary structure elements of DNA have been used successfully to protect short antisense DNA sequences against degradation by nucleases present in blood serum. In this project short hairpins and other structural elements of DNA was used to protect the 3' and 5' end of Dz's in two rounds of design.