(PDF) Gene therapy: A comprehensive review

Patil S. R. et al.

364

ery. Several gene therapy protocols for AIDS have been approved.

Elimination of virus from an infected person is an unlikely eventu-

ality, therefore the aims must be to maintain the virus in its latent period

as long as possible and to protect uninfected cells from viral infection

and perhaps to enhance the immune response against virus. These meth-

odologies are particularly amenable to a gene therapy approach and it

seems likely that in future the combination therapy including both phar-

nmacological agents and gene therapy agents, will be used in concert to

minimize this spread of the HIV with in an infected individual and thus

prolong their disease free life.A gene therapy based vaccine is also a

serious possibility.

8) Cancer26)

Several approaches to cancer therapy are being explored

1) Immune responses to tumors are being enhanced

2) Genes are being inserted into tumor cells to evoke cell suicide

3) Finally methods are being developed to modify tumor suppressor

or anti-oncogenes.

The primary target for stimulating an immune response to a tumor is

major histocompatability complex(MHC) class1-restricted tumor specif-

ic cytotoxic (CD8) T cell.

Two criteria must be met

1) The CD8 T cell receptors must be occupied by an MHC class 1

peptide complex

2) A helper T cell must be activated to secrete cytokines, which acts

on CD 8 T cell.

This second signal could be bypassed by inducing CD 8 cell to pro-

duce their own cytokines.

Cell suicide involves insertion of Herpes simples virus thymidine

kinase (HSV-TK) gene. Tumar suppressor genes are being inserted into

human tumors. One protocol involves inserting a normal p53 gene inot

non-small cell lung carcinomas that are p53 defective.

In another, antisense DNA is injected to try to suppress the activity

of activated oncogenes, in this case k-ras in lung carcinoma.

9) Gene Therapy and Viral Vaccination27)

Live viral vaccines have had a major impact on the incedence of

acute viral infections world-wide. Virus infections recognize as future

vaccine targets will require a modified approach based on the detailed

understanding of the immunobiology of specific infections combined

with the application of the new technologies designed to generate spe-

cific and appropriate protective immunity. A similar vector technology

directed at in vivo gene delivery is currently being exploited both gene

therapy and vaccination. The induction of an immune response to an

expressed transgene represents potential hazards for a gene therapy pro-

tocol but is the object of a vaccine strategy. In Vivo gene delivery using

replication-competent or replication-deficient viral vector systems and

by direct transfer of naked DNA can generate an effective humoral, sec-

retary and cell mediated immune response to expressed transgenes.

10) Also Gene therapy is a serious consideration in many

diseases caused by Virus, Bacteria and other microorgan-

isms.

FUTURE OF GENE THERAPY

To cure genetic diseases, scientists must first determine which gene

or set of genes causes each disease. The Human Genome Project and

other international efforts have recently completed the initial work of

sequencing and mapping virtually all of the 30,000 genes in the human

cell. This research will provide new strategies to diagnose, treat, cure,

and possibly prevent human diseases17).

Although this information will help scientists determine the genetic

basis of many diseases, it will be a long time before diseases actually

can be treated through gene therapy. "The Human Genome Project is

just a start," Nicholson says. "It's going to locate genes for us, but it's

not going to tell us what these genes do. That will be the next step. Once

we have that information, we'll be able to take advantage of that knowl-

edge to provide treatment and/or cures28)."

Gene therapy's potential to revolutionize medicine in the future is

exciting, and its expectations for curing and preventing childhood dis-

eases are encouraging. One day it may be possible to treat an unborn

child in utero for a genetic disease even before it comes in to this

world29).

Scientists are hoping, the mapping of the human genome will lead

the way toward cures for many diseases and that the successes of cur-

rent clinical trials will create new opportunities and challenges. For

now, however, it's a wait-and-see situation, calling for cautious opti-

mism.

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