the envelope protein needed to infect the human target cells.Treated with these two genomes, the packaging cell produces a crop of retroviruses with: an RNA copy of the retroviral gag, pol, and env genes but with no packaging signal (so these genes cannot be incorporated in fresh viral particles).inverted repeats (" R") at each end to aid insertion of the DNA copies into the DNA of the target cell.a packaging signal ( P) needed for the assembly of fresh virus particles.an RNA copy of the human ADA gene along with.Packaging cells are treated so they express:
RNA copies of the human ADA gene can be incorporated into the retroviral genome using a packaging cell.Their envelope protein enables the virus to infect human cells.Retroviruses have several advantages for introducing genes into human cells. It must be inserted in the DNA so that it will be expressed adequately that is, transcribed and translated with sufficient efficiency that worthwhile amounts of the enzyme are produced.Īll these requirements seem to have been met for SCID therapy using a retrovirus as the gene vector.So far, this means removing the patient's own cells, treating them in vitro, and then returning them to the patient. It must be inserted in cells that can take up long-term residence in the patient.The gene must be identified and cloned.This has been done for the ADA gene.what about giving the patient functioning ADA genes that is, gene therapy? Gene Therapy: requirements.But just like the insulin injections of a diabetic, they must be repeated at frequent intervals. When conjugated with polyethylene glycol (PEG) to delay its breakdown in the blood, ADA-PEG injections have kept SCID patients reasonably healthy. Give injections of ADA (the enzyme is currently extracted from cows).The virus was still present in the cells she donated, and killed her brother. (David received a bone marrow transplant from his sister, but she, like many people, had been infected earlier with the Epstein-Barr virus (the cause of "mono")). the donor cells may be infected with a virus which could overwhelm the recipient before his or her immune system was restored.even though the child cannot reject the transplant (the child has no immune system), T cells in the transplant (unless the donor was an identical twin) can attack the cells of the child producing graft-versus-host disease.Ideally, this would give the child a continuous source of ADA + T and B cells. Give the child a transplant of bone marrow from a normal, histocompatible, donor.David, the "bubble boy" from Houston, survived this way until he was 12 years old. Raise the child in a strictly germfree environment: all food, water, and air to be sterilized.
The normal catabolism of purines is deficient, and this is particularly toxic for T cells and B cells. It is a disease of young children because, until recently, the absence of an immune system left them prey to infections that ultimately killed them.Ībout 25% of the cases of SCID are the result of the child being homozygous for a defective gene encoding the enzyme adenosine deaminase ( ADA). SCID is a disease in which the patient has neither The prospects of gene therapy in these cases seems far more remote.Ĭase study: severe combined immunodeficiency (ADA-SCID) Other diseases also have a genetic basis, but it appears that several genes must act in concert to produce the disease phenotype. (The inheritance is recessive so both the maternal and paternal copies of the gene must be defective.) Is there any hope of introducing functioning genes into these patients to correct their disorder? Probably. Many human diseases are caused by defective genes.Īny one of several genes fail to make a protein essential for T and B cell functionĪll of these diseases are caused by a defect at a single gene locus.
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