Gene Therapy Works Better When RNA Replaces DNA

They then used modified these mRNAs as the basis for gene therapy treatment in two mouse models. In one set of experiments, mice received a single injection of mRNAs coding for the hormone erythropoietin. In the second set of experiments mice with a lethal congenital lung defect, caused by inability to make surfactant protein B (SP-B), were treated with regular applications of mRNA for SP-B as an aerosol.

Results published in the February 7, 2011, issue of the journal Nature Biotechnology revealed that a single intramuscular injection of modified mouse erythropoietin mRNA raised the average hematocrit in mice from 51.5% to 64.2% after 28 days. In a mouse model of a lethal congenital lung disease caused by a lack of surfactant protein B (SP-B), twice weekly local application of an aerosol of modified SP-B mRNA to the lung restored 71% of the wild-type SP-B expression.

"These results clearly demonstrate the therapeutic potential of our mRNAs,” said senior author Dr. Carsten Rudolph, professor of pediatrics at the University of Munich. "Chemical modification of the mRNA prevents it from activating the immune system, so that no inflammatory reaction ensues. Furthermore, in contrast to conventional mRNA, the modified mRNA can be administered repeatedly, is more stable, and is effective at very low doses.”

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