Indications in gene therapy clinical trials. The chart divides clinical gene transfer studies by disease classification. A majority of trials have addressed cancer, with monogenic disorders and cardiovascular diseases the next largest categories. (Reproduced with permission from J Gene Med. New Jersey, Wiley, 2006.) Gene Transfer for Genetic Disease Gene transfer strategies for genetic disease generally involve gene addition therapy. This approach most commonly involves transfer of the missing gene to a physiologically relevant target cell. . | Chapter 065. Gene Therapy in Clinical Medicine Part 2 Figure 65-1 Q Cancer diseases 67 n 797 Q Vascular diseases n .1O6 Q Monogenic diseases 8-8 n 1O2 Q infectious diseases rj-73 2 Olher diseases rr-4D Q Gena marking r 50 O Healthy volunteers 1 6 n l9 Source Feud AS. Ktipar OL írcunvcld E. H uitr SL. -Lento DL JL Lorcilto h Prirreiplts rrt3f iTth Editioni http vir .4o Copïrtflht OTM HtQr W-HlH ComporUCi. int All rtfltltf . Indications in gene therapy clinical trials. The chart divides clinical gene transfer studies by disease classification. A majority of trials have addressed cancer with monogenic disorders and cardiovascular diseases the next largest categories. Reproduced with permission from J Gene Med. New Jersey Wiley 2006. Gene Transfer for Genetic Disease Gene transfer strategies for genetic disease generally involve gene addition therapy. This approach most commonly involves transfer of the missing gene to a physiologically relevant target cell. However other strategies are possible including supplying a gene that achieves a similar biologic effect through an alternative pathway . factor VIIa for hemophilia A supplying an antisense oligonucleotide to splice out a mutant exon if the sequence is not critical to the function of the protein as has been done with the dystrophin gene in Duchenne muscular dystrophy or downregulating a harmful response through an siRNA. Two distinct strategies are used to achieve long-term gene expression one is to transduce stem cells with an integrating vector so that all progeny cells will carry the donated gene the other is to transduce long-lived cells such as skeletal muscle or neural cells. In the case of long-lived cells integration into the target cell genome is unnecessary provided the donated DNA can be stabilized in an episomal form. Immunodeficiency Disorders Proof of Principle Early attempts to provide gene replacement into hematopoietic stem cells HSCs were stymied by
