Application of improved GalNAc conjugation in development of cost-effective siRNA therapies targeting cardiovascular diseases.

N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases. By attaching a novel pyran-derived scaffold to serial monovalent GalNAc units before solid-phase oligonucleotide synthesis, we achieved increased GalNAc-siRNA production efficiency with fewer synthesis steps compared to the standard triantennary GalNAc construct L96. The improved GalNAc-siRNA conjugates demonstrated equivalent or superior in vivo efficacy compared to triantennary GalNAc-conjugated siRNAs.

[Reduction in cost of stay in intensive care unit with price education program of drugs].

OBJECTIVE: To study if the cost of stay in intensive care unit (ICU) could be reduced by educating intensivists with price of drugs used in ICU. METHODS: A ten-bed ICU of a teaching hospital, with admittance of about 40 patients every month, was involved, and cost of stay was charged by computer system, and it could be calculated and checked by computer on line. Firstly, the knowledge of the prices of 100 drugs usually used in ICU among the 7 intensivists was investigated, then an education program of drug price was launched to train the 7 intensivists,and they were urged those the drugs with lower price instead of higher price treatment results .Finally, the cost of stay in ICU for 2 months before and after the education program was analyzed and their difference was compared. RESULTS: The intensivists understood only the prices of 18% of drugs used in ICU. The cost of drugs was reduced by 8.6% during 2 months after education program (31.8%) compared with that before education program (40.4%), but there was no significant statistical difference (P>0.05). However, the cost of clinical examinations and check-up was lower after education than that before education (P<0.01). The total cost of stay in ICU was 5,688 yuan each day before education program and 5,267 yuan after education program. The total cost daily was reduced by 421 yuan, but with no significant statistical difference (P>0.05). CONCLUSION: The price education program of drugs can reduce the expense of drug and total cost of stay in ICU.