Applications and developments of gene therapy drug delivery systems for genetic diseases

Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity.Currently,gene therapy drugs such as siRNA,shRNA,antisense oligonucleotide,CRISPR/Cas9 system,plasmid DNA and miRNA have shown great potential in biomedical applications.To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues,cells and organelles,the development of excellent drug delivery vehicles is of utmost importance.Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression.With the development of nanotechnology,novel nanocarriers are gradually replacing viral vectors,emerging superior performance.This review mainly illuminates the current widely used gene therapy drugs,summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs,and sums up the application of gene therapy to treat genetic diseases.Additionally,the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.

Distribution of C - myc Antisense Oligonucleotides in Rabbits after Local Delivery by Implanted Gelatin Coated Platinium - Iridium Stent

Objectives To assess thefeasibility, efficiency and tissue distribution of local delivered c - myc antisense oligonucleotides (ASODN) by implanted gelatin coated Platinium - Iridium (Pt -Ir) stent. Methods Gelatin coated Pt - Ir stent which absorbed carboxyfluorescein - 5 - succimidyl ester (FAM) labeled c - myc ASODN were implanted in the right carotid arteries of 6 rabbits under vision. Blood samples were collected at the indicated times. The target artery, left carotid artery, heart , liver and kidney obtained at 45 minutes , 2 hours and 6 hours. The concentration of c - myc ASODN in plasma and tissues were determined by Thin Layer Fluorome-try. Tissue distribution of c - myc ASODN were assessed by fluorescence microscopy. Results At 45 min, 2 h, 6 h, the concentration of FAM labeled c -myc ASODN in target artery was 244. 39, 194. 44, 126. 94(μg/g tissues) respectively, and the delivery efficiency were 44. 4% , 35. 4% and 23. 1% respectively. At the same indicated time point, the plasma concentration was 8. 41, 5. 83, 14. 75 (μg/ml) respectively. Therefore c - myc ASODN concentrations in the target vessel were 29, 33 and 9 -fold higher than that in the plasma. There was circumferential distribution of labeled c - myc in the area of highest fluorescein coinciding with the site of medial dissecting from stent-ing, and the label was most intense in target vessel media harvested at 45 min time point and then dispersed to adventitia. Conclusions Gelatin coated Pt - Ir stent mediated local delivery of c - myc ASODN is feasible and efficient. The localization of ASODN is mainly in target vessel wall.