A new approach to gene therapy.
Since 1975, different virus vectors have been developed in order to carry functional genes for gene transfer. However, no successful clinical trials have been reported so far. Recently, a new method for altering a single basepair of target DNA was reported using chimeric RNA/DNA oligonucleotides. The replacement of the single basepair in the target sequence can reach an efficacy of 20%. In patients with hemophilia A or B, the mutations (coagulation factors VIII and IX) are well characterized. The mutation-repair method using chimeric RNA/DNA oligonucleotides could provide an alternative for the treatment of hemophilia. The repaired cells will produce normal protein, like that of non-mutated cells, and the expression of the protein will be stable as long as the repaired cells survive. Clinically, by increasing the concentration of the functional protein (5-10%), it is hoped that a severe phenotype can be converted into a milder phenotype. The high replacement efficacy of the target sequence and the safety of the method make this a likely and promising approach for gene therapy in the future. However, no correction has been detected for the mutations in the coagulation factor genes factor genes factor IX and von Willebrand factor by this method so far.
Zhang
Z
Z
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Eriksson
M
M
Blombäck
M
M
Anvret
M
M
D000818:Animals; D018390:Gene Targeting / Q000379:methods / Q000639:trends; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends*; D006467:Hemophilia A / Q000235:genetics / Q000628:therapy; D002836:Hemophilia B / Q000235:genetics / Q000628:therapy; D006801:Humans; D014842:von Willebrand Diseases / Q000235:genetics / Q000628:therapy