Genetically engineered pharmaceuticals

DEFINITION: Drugs created through the manipulation of genetic materials

Genetic technology is being used to develop state-of-the-art drugs to treat human diseases and health conditions. Genetic engineering can create carefully targeted drugs that offer greater effectiveness and potency than conventional pharmaceuticals while causing fewer side effects.

Genetics is the scientific study of heredity—the biological factors that determine the characteristics of all living things. All reproductive life-forms develop under the laws of genetics. The basis of genetics is the gene, a tiny unit of matter that determines some identifiable characteristic of an individual. Genes are located in fixed positions on chromosomes (molecular chains) that reside in the center of cells. A major part of the chromosome is deoxyribonucleic acid (DNA), which is responsible for transmitting genetic information, in the form of genes, when new life is created. This transfer of traits applies to organisms of all sizes, from microscopic to larger and more complex systems, such as humans. Inherited traits include color of hair, eyes, and skin, as well as susceptibility to various ailments.

As the complex chemical-biological process of reproduction takes place at the gene-chromosome level, it is possible for a random processing error called a mutation to be introduced. Mutant cells may cause many human defects and diseases. Genetic abnormalities, also known as birth defects, include such ailments as hemophilia (resistance to blood clotting), color blindness, anatomical defects, speech disorders, hormonal disorders, brain disorders, and psychiatric illness. Aside from birth defects, genetic cellular mutations can occur anytime during a lifetime. Normally the body contains certain controlling genes that destroy mutant genes that spontaneously appear. If these controlling genes become defective, the mutant genes can take over the body, as occurs with cancerous tumors.

Genetic Technology in Medicine

Pharmaceuticals are drugs used to treat human diseases and conditions. The term “engineered drug” implies that scientific principles and manufacturing processes are applied in creating the drug. A genetically engineered pharmaceutical is a specialized drug made by the application of specific genetic principles. Gene-based technology is used to investigate, test, and apply state-of-the-art pharmaceuticals to invasive and widespread diseases. Its potential for fighting illnesses such as cancer and acquired immunodeficiency syndrome (AIDS) is of particular interest to medical science.

For example, scientists have developed ways to control cancer cells using genetic medicines instead of killing the cancer with radiation, conventional drugs, or surgical removal. Herceptin, a genetically engineered drug approved by the U.S. Food and Drug Administration (FDA), is used in treating certain breast cancers. Herceptin is an antibody engineered to attack specific cancer cells, helping to reduce the cancer tumor by keeping a particular protein from reproducing. Some tumor cells are inherently resistant to the drug or become resistant over time.

In the past, the production of natural body chemicals required the harvesting of the needed chemicals from human or animal materials. Supplies of such sources are sometimes minimal, and concentrating chemicals from human and animal tissue can also multiply the chances of carrying diseases from those sources. For instance, during the 1960s through the mid-1980s, some children suffering from growth failure were treated with human growth (HGH) extracted from the pituitary glands of human cadavers. In 1985, three adults in the United States who had been treated with this HGH during childhood died from Creutzfeldt-Jakob disease (CJD), a rare, incurable, and fatal brain disease with a long incubation period. Other recipients of HGH, both in the United States and abroad, also contracted CJD, apparently from HGH that was contaminated with the that causes CJD.

Genetic engineering of substances such as growth hormone circumvents many traditional problems. The genes for producing the desired chemicals can be implanted in the genetic code of plants or microorganisms, especially the benign bacterium Escherichia coli. These sources can enable high-volume production at high levels of concentration. Because plants and microorganisms are very different from people, the chance of spreading disease through this production method is minimal.

Genetically Engineered Vaccines

Genetically engineered pharmaceuticals can increase the body’s production of naturally occurring chemical substances and supply toxins to attack targeted pathogens (disease-causing viruses, bacteria, fungi, or parasites). Vaccines work by triggering the body’s immune system, which then defends itself. Compared with traditional methods of creating vaccines, enables faster development of safer vaccines.

A live attenuated vaccine is one that contains the living pathogen, but in a weakened form that cannot induce illness. Recombinant DNA technology can be used to remove key genes from microbes to render them harmless. This method has been used to engineer a vaccine against Vibrio cholerae, the bacterium that causes cholera. Another live attenuated vaccine, one used against the rotavirus responsible for serious diarrheal illness in infants and young children, was created through a technique that combines genes from different strains of the pathogen in a way that makes a harmless simulator virus. In 2020, genetic engineering was used to create mRNA vaccines to combat the COVID-19 virus. In the wake of the success of the vaccines, research into further mRNA-based vaccines and treatments took a giant step forward in the early 2020s, with numerous clinical trials and applications under study. Additionally, advanced malaria vaccines were produced to better control the Plasmodium falciparum infection globally. At the cellular or molecular level, the simulator appears to the immune system to be a pathogenic invader, causing antibodies to develop that attack the active pathogen.

A subunit vaccine does not employ the entire pathogenic organism; rather, it relies on its antigens, substances that trigger the body’s immune system. For this technique, select antigens or portions thereof are used to provoke an immune response. While the antigens could be harvested from laboratory-grown microbes, recombinant DNA technology makes it possible to manufacture the antigen molecules. These parts of the pathogen’s genetic code are inserted into common baker’s yeast, a harmless microbe. Hepatitis B subunit vaccine uses a portion of the protein coat surrounding the virus’s DNA. Because the rest of the microbe is not included, the possibility of an adverse reaction is greatly reduced.

In the creation of conjugate vaccines, the bacterial antigens selected for the immune response they provoke are not easily recognized by the body. These are joined with easily recognizable antigens located on a harmless bacterial shell and injected into the body to trigger the immune system. Conjugate vaccines for children have been developed against middle-ear infections and other diseases caused by pneumococci, a group of common bacteria. In 2000, the FDA licensed Prevnar, a conjugate vaccine that targets the seven most common types of pneumococci causing invasive disease in infants and toddlers. Ten years later, with other types of pneumococci becoming increasingly common in young children, the FDA licensed a conjugate vaccine to replace Prevnar, one that targets thirteen pneumococcal strains.

Naked DNA vaccines have been tested on diseases such as AIDS and some cancers. This experimental method involves injecting a person with some of a pathogen’s DNA—specifically, with the genes that code for antigens. Some of the body’s cells accept this added DNA as instructions to produce antigens, thereby triggering immune response. A similar experimental technique, recombinant vaccination, employs attenuated microorganisms that act as carriers for the DNA while further stimulating immune response.

The use of genetically engineered pharmaceuticals has raised concerns about their possible effects on the environment. In 1989, the Virginia Department of Health approved a field test of baits spiked with genetically engineered oral vaccine to control the spread of rabies in raccoons. Health officials were worried, however, about the possible danger to humans posed by the vaccinia virus used as the vaccine; thus, an island location was chosen to prevent the possible spread of vaccinated animals to larger, mainland populations. Several researchers expressed concerns about the long-term effects of releasing a nonnative virus into the environment; although vaccinia had been used for many years to prevent smallpox, little was known about its host range or its ability to cause disease. The U.S. Department of Agriculture concluded in a 1991 report, however, that laboratory and field tests had shown the genetically engineered rabies vaccine to have had no adverse effects on any species. In the same report, the department approved further field tests on the grounds that such tests were safe and posed no significant environmental risk. This rabies-control method has since become common practice in North America and Europe.

Bibliography

Aldridge, Susan. The Thread of Life: The Story of Genes and Genetic Engineering. 1996. Reprint. New York: Cambridge University Press, 2000.

Castilho, Leda R., et al., eds. Animal Cell Technology: From Biopharmaceuticals to Gene Therapy. New York: Taylor & Francis, 2008.

Crommelin, Daan J. A., et al. Pharmaceutical Biotechnology: Fundamentals and Applications. 5th ed. Springer, 2019.

Gad, Shayne Cox, ed. Handbook of Pharmaceutical Biotechnology. Hoboken, N.J.: John Wiley & Sons, 2007.

Groves, M. J., ed. Pharmaceutical Biotechnology. 2d ed., Taylor & Francis, 2006.

Guzman, Carlos Alberto, and Giora Z. Feuerstein, eds. Pharmaceutical Biotechnology. New York: Springer, 2009.

Murphy, Sean C., et al. “A Genetically Engineered Plasmodium Falciparum Parasite Vaccine Provides Protection from Controlled Human Malaria Infection.” Science Translational Medicine, vol. 14, no. 659, 2022, doi.org/10.1126/scitranslmed.abn9709. Accessed 19 July 2024.

Pfeifer, Blaine A., et al. "Harnessing Synthetic Biology for Advancing RNA Therapeutics and Vaccine Design." npj Systems Biology and Applications, vol. 9, no. 60, 2023, doi.org/10.1038/s41540-023-00323-3. Accessed 19 July 2024.

Rehbinder, E., et al. Pharming: Promises and Risks of Biopharmaceuticals Derived from Genetically Modified Plants and Animals. Berlin: Springer, 2009.

Walsh, Gary. Biopharmaceuticals: Biochemistry and Biotechnology. 2d ed., John Wiley & Sons, 2003. pharmareview.files.wordpress.com/2015/03/biopharmaceuticals-biochemistry-and-biotechnology-walsh-wiley-2e-2003.pdf. Accessed 19 July 2024.