An in vivo model of somatic cell gene therapy for human severe combined immunodeficiency.
Deficiency of adenosine deaminase (ADA) results in severe combined immunodeficiency (SCID), a candidate genetic disorder for somatic cell gene therapy. Peripheral blood lymphocytes from patients affected by ADA- SCID were transduced with a retroviral vector for human ADA and injected into immunodeficient mice. Long-term survival of vector-transduced human cells was demonstrated in recipient animals. Expression of vector-derived ADA restored immune functions, as indicated by the presence in reconstituted animals of human immunoglobulin and antigen-specific T cells. Retroviral vector gene transfer, therefore, is necessary and sufficient for development of specific immune functions in vivo and has therapeutic potential to correct this lethal immunodeficiency.
Ferrari
G
G
Laboratory of Hematology, Istituto Scientifico H.S. Raffaele, Milano, Italy.
Rossini
S
S
Giavazzi
R
R
Maggioni
D
D
Nobili
N
N
Soldati
M
M
Ungers
G
G
Mavilio
F
F
Gilboa
E
E
Bordignon
C
C
D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000628:therapy; D019868:Kanamycin Kinase; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009841:Oligonucleotides / Q000737:chemistry; D010770:Phosphotransferases / Q000235:genetics; D016133:Polymerase Chain Reaction; D012190:Retroviridae / Q000235:genetics
D009841:Oligonucleotides; D010770:Phosphotransferases; D019868:Kanamycin Kinase; D000243:Adenosine Deaminase