| 摘要 |
<p>Eukaryotic mRNA that encodes a protein of therapeutic interest is stabilised by at least one chemical modification. The stabilisation of the mRNA permits its use in sense RNA therapy wherein therapeutic proteins of interest are expressed transiently in cells. Modifications include 3' blocking, 5' blocking, a modified diguanosine (m7) cap linked to the mRNA by a chemically modified linkage, a 2' modified oligonucleotide, a poly A tail of greater than 50 bases in length, or a phosphorothiorate modification. Various disease states may be treated using such modified sense RNAs expressing relevant therapeutic proteins, including cystic fibrosis; muscular dystrophy; sickle cell anemia; thalasemia, coronary arterary disease, cancer, inflammation, stroke, heart disease, thrombosis, anemia, spinal-muscular atrophy, epilepsey, wound healing, septic shock, asthma, viral infection, bacterial or parasitic infection, diabetes, metabolic diseases, urea cycle disorders, Gaucher, schizophrenia, depression, Parkinson's disease, renal failure, liver failure, arthritis, impotence, baldness, pain, ulceration, and enlarged prostate.</p> |
