Biomedical Engineering Reference
In-Depth Information
numbers in culture, and about 10 10 cells were then reinfused. Due to the limited life
span of lymphocytes, this treatment was repeated at 1.5-month intervals.
Another ideal treatment was to transduce HSCs that continuously give rise to lym-
phocytes, to provide long-term treatment of ADA deficiency. However, animal stud-
ies have indicated the difficulty of transducing stem cells. Recently, the targeting of
HSCs from cord blood of neonates with ADA deficiency showed that these cells are
suitable targets for efficient gene transfer [175] .
5.4.3.3 Cancer
Generally, the current gene therapy emphasizes treating cancer by stimulating the immune
response against the cancer cells. In one report, genes that encode new antigens are trans-
ferred into some of the cancer cells to stimulate an immune response from these new
antigens and also from minor antigens expressed by all of the cancer cells [176] . Another
alternative approach that involves the production of immunostimulatory cytokines within
tumors is the transfer of genes either into the tumor cells or into cells such as fibroblasts
that can be easily injected into the tumor. Retroviral vectors have a major advantage for
this cancer treatment, in that they can efficiently transduce primary cells, which are often
difficult to grow, and they cause the transduced gene to be expressed at high levels. Direct
injection of DNA or DNA-lipid mixtures (lipofection) into tumors is also being used as
an alternative therapy, but none of these treatments have yet been shown to be effective.
Clinical trials of gene therapy for treatment of brain tumors are also underway [177] .
5.4.3.4 AIDS
For the treatment of AIDS, retroviral vectors provide a method that can be used for
gene delivery to suitable cell types, including CD4-positive T cells that are the tar-
gets for infection, or progenitor cells, including HSCs that give rise to T cells. The
transfer of Rev dominant-negative mutant proteins and anti-HIV ribozymes has been
approved for testing in humans by the U.S. Recombinant DNA Advisory Committee
for the inhibition of HIV replication in T lymphocytes. But possibly the best strategy
would involve transfer of genes that would protect cells from infection by HIV. Such
types of cell protection might be provided by synthesis of peptides that block HIV
binding and entry at the level of the cell surface receptor for HIV. Mice and chickens
that express fragments or complete retroviral env proteins derived from endogenous
virus that cannot, and do not, provoke an immune response, can be protected against
infection by the corresponding avian or MLV [178,179] . Another approach involves
antisense RNAs or ribozymes that block reverse transcription or integration of HIV.
5.5 Herpes Simplex Virus
5.5.1  Structure and Biology of Herpes Simplex Virus
Herpes simplex virus 1 and 2 (HSV-1 and -2), also known as human herpes virus 1
and 2 (HHV-1 and -2). HSV-1 and -2 are two members of the herpes virus family,
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