A new approach to gene therapy. 1997

Z Zhang, and M Eriksson, and M Blombäck, and M Anvret
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.

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.

UI MeSH Term Description Entries
D002836 Hemophilia B A deficiency of blood coagulation factor IX inherited as an X-linked disorder. (Also known as Christmas Disease, after the first patient studied in detail, not the holy day.) Historical and clinical features resemble those in classic hemophilia (HEMOPHILIA A), but patients present with fewer symptoms. Severity of bleeding is usually similar in members of a single family. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma. Treatment is similar to that for hemophilia A. (From Cecil Textbook of Medicine, 19th ed, p1008) Christmas Disease,Factor IX Deficiency,Deficiency, Factor IX,F9 Deficiency,Haemophilia B,Hemophilia B Leyden,Hemophilia B(M),Plasma Thromboplastin Component Deficiency,Bs, Hemophilia,Deficiencies, F9,Deficiencies, Factor IX,Deficiency, F9,Disease, Christmas,F9 Deficiencies,Factor IX Deficiencies,Haemophilia Bs,Hemophilia Bs,Hemophilia Bs (M)
D006467 Hemophilia A The classic hemophilia resulting from a deficiency of factor VIII. It is an inherited disorder of blood coagulation characterized by a permanent tendency to hemorrhage. Factor VIII Deficiency,Hemophilia,Autosomal Hemophilia A,Classic Hemophilia,Deficiency, Factor VIII,Factor 8 Deficiency, Congenital,Factor VIII Deficiency, Congenital,Haemophilia,Hemophilia A, Congenital,Hemophilia, Classic,As, Autosomal Hemophilia,Autosomal Hemophilia As,Classic Hemophilias,Congenital Hemophilia A,Congenital Hemophilia As,Hemophilia A, Autosomal,Hemophilia As,Hemophilia As, Autosomal,Hemophilia As, Congenital,Hemophilias, Classic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014842 von Willebrand Diseases Group of hemorrhagic disorders in which the VON WILLEBRAND FACTOR is either quantitatively or qualitatively abnormal. They are usually inherited as an autosomal dominant trait though rare kindreds are autosomal recessive. Symptoms vary depending on severity and disease type but may include prolonged bleeding time, deficiency of factor VIII, and impaired platelet adhesion. Angiohemophilia,Hemophilia, Vascular,von Willebrand Disease,Vascular Pseudohemophilia,Von Willebrand Disorder,Von Willebrand's Factor Deficiency,von Willebrand Disease, Recessive Form,von Willebrand's Disease,von Willebrand's Diseases,Angiohemophilias,Disorder, Von Willebrand,Pseudohemophilia, Vascular,Pseudohemophilias, Vascular,Vascular Hemophilia,Vascular Hemophilias,Vascular Pseudohemophilias
D015316 Genetic Therapy Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions. Gene Therapy,Somatic Gene Therapy,DNA Therapy,Gene Therapy, Somatic,Genetic Therapy, Gametic,Genetic Therapy, Somatic,Therapy, DNA,Therapy, Gene,Therapy, Somatic Gene,Gametic Genetic Therapies,Gametic Genetic Therapy,Genetic Therapies,Genetic Therapies, Gametic,Genetic Therapies, Somatic,Somatic Genetic Therapies,Somatic Genetic Therapy,Therapies, Gametic Genetic,Therapies, Genetic,Therapies, Somatic Genetic,Therapy, Gametic Genetic,Therapy, Genetic,Therapy, Somatic Genetic
D018390 Gene Targeting The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. Gene Targetings,Targeting, Gene,Targetings, Gene

Related Publications

Z Zhang, and M Eriksson, and M Blombäck, and M Anvret
November 2000, Chinese journal of traumatology = Zhonghua chuang shang za zhi,
Z Zhang, and M Eriksson, and M Blombäck, and M Anvret
November 2017, Nature reviews. Neurology,
Z Zhang, and M Eriksson, and M Blombäck, and M Anvret
November 1989, Circulation,
Z Zhang, and M Eriksson, and M Blombäck, and M Anvret
June 2010, Journal of drug targeting,
Z Zhang, and M Eriksson, and M Blombäck, and M Anvret
March 1995, Cancer control : journal of the Moffitt Cancer Center,
Z Zhang, and M Eriksson, and M Blombäck, and M Anvret
May 1951, Journal of the National Association of Chiropodists,
Z Zhang, and M Eriksson, and M Blombäck, and M Anvret
June 1964, Applied therapeutics,
Z Zhang, and M Eriksson, and M Blombäck, and M Anvret
April 1968, Lancet (London, England),
Z Zhang, and M Eriksson, and M Blombäck, and M Anvret
March 1968, Lancet (London, England),
Z Zhang, and M Eriksson, and M Blombäck, and M Anvret
October 1995, Medical hypotheses,
Copied contents to your clipboard!