NapaJen Pharma, Inc.

Aptamers are an attractive candidate for a molecular-targeted drug since they can show ability to precisely recognize proteins with a large affinity similar to antibodies. A drawback of aptamers is that they can be easily degraded under biological conditions by DNase (or RNase). In this study, we attached poly(dA) tail to the 3′ end of thrombin DNA aptamer and found that its survival time in human plasma was prolonged by about threefold compared to the original aptamers (i.e., without the tail). We found that the attachment of a poly(dA) tail at the 3′ end caused an increase of the clotting inhibitory activity. A preliminary in vivo assay using BALB/c mice confirmed a considerably elongated clotting time for the tailed aptamer. When the poly(dA) tail was attached to three other DNA aptamers, DNase resistance was increased, indicating that the present finding can be universally applied to increase stability of DNA aptamers.

We have developed a technol. platform for specifically targeting oligonucleotide drugs to dendritic cells (DC) and macrophages, by complexing the drugs with Schizophyllan (SPG) a beta-glucan that interacts with Dectin-1, a mammalian receptor for glucans predominantly expressed on DC and macrophages.These are first responder antigen presenting cells that play critical roles in oncol., autoimmune, inflammatory, infectious disease and transplantation settings.By complexing an oligonucleotide targeting the mRNA of the co-stimulatory mol. CD40 with SPG, we have achieved permanent allograft acceptance in a murine cardiac transplantation model through short-term peri-transplant administration.We further report having attained low dose efficacy, through integrating Dectin-1 receptor-mediated precision delivery with stability enhancement conferred onto the oligo drug by SPG.Based on these results, a brief overview of our pipeline program will also be presented.

A review.In this paper, we will introduce the outline of the technol. to be developed based on the problems of nucleic acid medicine, the value provided by our company, the unique technol. and ideas that support it, and the future development.