December 22, 2010

Role of recombinant DNA technology in disease prevention....(Article Volume#49)

THE MOST human protein pharmaceuticals are available in only limited quantities. They are costly to produce and in a number of cases their biological mode of action is not well-characterized. Many infectious and fatal diseases are very difficult to be treated by these pharmaceuticals. So the need of the hour is that to develop such techniques that help the human beings in developing the drugs with cheap rates and also having good efficiencies. In this regard, Recombinant DNA Technology has been evolved as a revolutionary science.

Plant-derived pharmaceuticals are poised to become the next major commercial development in biotechnology. The advantages they offer in terms of production scale and economy, product safety, ease of storage and distribution cannot be matched by any current commercial system. They also provide the most promising opportunity to supply low-cost drugs and vaccines to the developing world like Pakistan. Thus modern biotechnology helps the human beings in various ways such as disease prevention, disease treatment, gene therapy and immune-deficiencies etc.

Disease Prevention:-

Vaccination protects a recipient from pathogenic agents by establishing an immunological resistance to infection. An injected or oral vaccine induces the host to generate antibodies against the disease-causing organism; therefore, during exposure, the infectious agent is inactivated (neutralized or killed), its proliferation is prevented and the disease state is not established.

Commercial diseases such as tuberculosis, small pox, cholera, typhus etc have been a scourge for humankind. With the advent of vaccination, antibiotics and effective public health measures, these epidemic diseases have been brought under control. Occasionally, however, protective measures become ineffective, and devastating new outbreaks occur. Also, for many current human and animal diseases, there are no vaccines.

Today, over 2 billion humans suffer from diseases that theoretically could be curtailed by vaccination. In addition, new diseases for which vaccines might be useful continue to emerge.

Conventional vaccines:-

Conventional vaccines consist of whole pathogenic organisms which may either be killed (most bacterial vaccines and some viral vaccines) or live (hence called live vaccines); the virulence of pathogens is greatly reduced (attenuation).

Traditionally, the infectious agent is grown in culture, purified and either inactivated or attenuated without of course, losing the ability to evoke an immune response that is effective against the virulent form of the infectious organism.

There are a number of limitations in traditional mode of vaccination production.

• Not all infectious agents can be grown in culture, and so no vaccines have been developed for a number of diseases.

• Both the yield and rate of production of animal and human viruses in culture are often quite low, thereby vaccine production becomes costly.

• Extensive safety precautions are necessary to ensure that laboratory and production personnel are not exposed to any pathogenic agent.

• Not all diseases are preventable through the use of traditional vaccines.

• Most current vaccines have a limited shelf life and often require refrigeration to maintain potency. This requirement creates storage problems in countries with large, unelectrified rural areas.

• Production of animal and human viruses requires animal cell culture, which is expensive.

• Batches of vaccine may not be killed or may be insufficiently attenuated during the production processes; therefore introducing virulent organisms into the vaccine may inadvertently spread the disease.

• Attenuated strains may revert, a possibility that requires continual testing to ensure that the reacquisition of virulence has not occurred. Modern vaccines:-

Within the last decade, recombinant DNA technology has provided a means of creating a new generation of vaccines that overcome the drawbacks of traditional vaccines. The availability of gene cloning has enabled researchers to contemplate various novel strategies for vaccine development. In this technology immunologically active, noninfectious agents are produced by deleting the genes that cause virulence. With this deletion, a live vaccine would never be able to revert to the infectious form.

A gene that encodes a major antigenic determinant from a pathogenic organism can be cloned into the genome by a benign carrier organism (usually a virus or bacterium), which can be used as a vector without concern that any pathogenic organism can be inserted into expression vectors and large amounts of the product can be harvested, purified and used as a vaccine.

Thus modern vaccines have overcome the drawbacks of traditional vaccines in following ways:

• Virulence genes could be deleted from an infectious agent that retains the ability to stimulate an immunological response. In this case, the genetically engineered agent could be used as a live vaccine without concern about reversion to virulence, because it is almost impossible for a whole gene to be reacquired spontaneously growth during pure culture.

• For infectious agents that cannot be maintained in culture, the genes for the proteins that have critical antigenic determinants can be isolated, cloned and expressed in an alternative host system such as Escherichia coli or a mammalian cell line. These cloned gene proteins can be formulated into a vaccine.

• There are some infectious agents that do not damage host cells directly; instead, the disease condition results when the host immune system attacks its own (infected) cells. For these diseases, it may be possible to create a targeted cell-specific killing system. Although not a true vaccine, this type of system attacks only infected cells, thereby removing the source of the adverse immunological response. In these cases, the gene for a fusion protein is constructed. First, one part of this fusion protein binds to an infected cell. Then, the other part kills the infected cells.

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