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Chapter 19 : Health Care Applications

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Health Care Applications, Page 1 of 2

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Abstract:

Throughout the 20th century, advances in imaging technology provided diagnostic tools that made invisible symptoms visible and helped physicians catch some diseases earlier. For example, new visualization techniques could reveal cancers before clinical symptoms appeared and sometimes before they had spread to other organs. Early intervention lessens the harmful impacts of the disease and may even provide an opportunity to cure the disease rather than simply manage it. Early detection and treatment of infectious diseases have important public health implications, as well. Biotechnology-based improvements in diagnosing human immunodeficiency virus (HIV) infections provide a striking example of the public health benefits of early detection. Although the relationship between genes and health is receiving more public attention now than ever before, using genetics as a diagnostic component of health care is not new. The link between genes and a certain disorder becomes increasingly vague and ambiguous when either many genes contribute to the disorder (multigenic disorder) or genes and environmental factors interact and lead to the disorder (multifactorial disorder). Gene therapy would use genes, or related molecules, such as RNA, to treat diseases. Rather than giving daily injections of missing or malfunctioning proteins, medical researchers dream of supplying patients with accurate instruction manuals-nondefective genes. The most familiar form of cell transplant therapy is the 20+-year practice of transplanting bone marrow cells into cancer patients. Medical scientists are excited about the prospect of using the body’s natural healing processes not simply to treat debilitating diseases but perhaps to cure them.

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19

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Immune System Proteins
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Transforming Growth Factor beta
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Figures

Image of Figure 19.1
Figure 19.1

Improvements in karyotyping techniques. Technological innovations can provide more detailed answers to an old question. Physicians have used karyotyping to identify genetic problems for many decades. () Using low-resolution micrographs, they could identify major chromosomal disorders, such as extra chromosomes, as in trisomy 21, which is associated with Down's syndrome. () Better microscopy techniques allowed them to observe banding patterns, which helped them identify certain chromosomal disorders, such as translocations or deletions, as long as a significant length of the chromosome had been altered. () Spectral karyotype paints (SKY), a new technique that utilizes DNA probes labeled with fluorescent dyes, permits the identification of much smaller genetic changes. () Computer-assigned colors, based on the fluorescent dyes, are easier to analyze. () A side-by-side comparison of a spectral karyotype and a standard black and white karyotype. (Photographs courtesy of the Pathology Department, University of Washington [A], and H. Padilla-Nash and T. Ried, Genetics Laboratory, National Cancer Institute, National Institutes of Health [B to E].)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.2
Figure 19.2

Disease diagnosis. () For centuries, the only available clues for diagnosing diseases were late-stage clinical symptoms that physicians could observe unaided. In this painting, the physician is attempting to diagnose asthma by using only his ear to hear the patient breathe. () In the early 1800s, physicians realized they could hear sounds in the lungs better by using a rolled up piece of paper. This led to the invention of a tube-like stethoscope by René Laënnec in 1830. () By 1880, the tube stethoscope had evolved into one that resembles the stethoscope physicians use today. The photograph in panel A, a reproduction of a painting by Theobald Chartan, was published in in 1853. (Photographs courtesy of the National Library of Medicine, National Institutes of Health [A], the National Museum of Health and Medicine, U.S. Armed Forces [B], and the National Museum of American History, Smithsonian Institution [C].)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.3
Figure 19.3

Imaging cancer. Lung X rays and mammograms allow physicians to detect cancer before clinical symptoms appear. () The bright spots show that the patient has cancer in the lung on the right side of the X ray. () The arrow points to a small tumor that may be breast cancer. (Photographs courtesy of National Cancer Institute, National Institutes of Health.)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.4
Figure 19.4

Monoclonal antibodies in cancer detection. Rather than surgically removing cells to determine whether a patient has cancer, physicians can use monoclonal antibodies that bind specifically to cancer cell surface antigens. In this imaging technique, researchers attach a radioactive isotope to monoclonal antibodies that bind to cancer cells. Radiolabeled antibodies confirm that the patient's cancer has spread to the lymph nodes, because radioactivity, indicated by dark areas, is detected in the lymph nodes of the armpits, neck, and groin. Not only does this technique remove the need for surgical biopsies, it also helps physicians identify the disease stage. In this image, the patient's liver and spleen are also darkened because all antibodies normally collect in those organs. () Frontal view. () Rear view. (Photograph courtesy of Jorge Carrasquillo, National Cancer Institute, National Institutes of Health.)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.5
Figure 19.5

AIDS diagnosis. HIV-infected individuals display clinical symptoms many years after being infected. The symptoms include the appearance of rare infectious diseases and uncommon cancers that are AIDS-defining illnesses. () A micrograph shows lymph nodes containing a tremendous number of bacteria (dark-pink rods) that usually infect birds, not humans. () Kaposi's sarcoma. (Photographs courtesy of Edwin Ewing, Centers for Disease Control and Prevention [A], and National Cancer Institute, National Institutes of Health [B].)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Figure 19.6

An antibody-based HIV diagnostic test. () Blood is drawn from two people. Patient 1 is infected, so the blood contains antibodies to HIV. () The patient's antibodies specifically bind to the purified HIV proteins in the diagnostic test. () The blood is washed off, but HIV antibodies stay bound to the HIV antigens. (but HIV antibodies stay bound to the HIV) In the final step, monoclonal antibodies with a fluorescent tag are added. These bind specifically to HIV antibodies. When the monoclonal antibody binds to an HIV antibody, the indicator tag fluoresces. The lack of fluorescence indicates a lack of HIV antibodies. According to this test, patient 1 is HIV positive. When the physician obtains a positive result, a different type of test is conducted to verify that the person is HIV infected.

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.7
Figure 19.7

Cancer and normal cells. () Human connective tissue. The large, variably shaped nuclei; small cytoplasmic volume compared to the nucleus; and loss of normal cell specialization features are all characteristic of cancer cells (right) compared to normal cells (left). (Photograph courtesy of Cecil Fox, National Cancer Institute, National Institutes of Health.) () Metastasis. Locomotion is integral to the metastasis process, and metastatic cancer cells develop long arms, or pseudopodia, for that purpose. Scientists have recently identified the protein that causes cancer cells to grow arms. (Scanning electron micrograph by Susan Arnold, courtesy of Raouf Guirgus, National Cancer Institute, National Institutes of Health.)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.8
Figure 19.8

Biomarkers. As normal cells accumulate mutations, changes in their molecular products such as mRNA and protein also occur. Identifying the biochemical changes can help physicians diagnose cancers much earlier. If they are able to identify precancerous cells, they may be able to prevent the cancer from developing.

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.9
Figure 19.9

Progress in disease diagnosis. A disease process begins with molecular and cellular changes, moves through a series of stages, and, in the later and more severe stages, becomes manifested as visible clinical symptoms. Technological advances in the 20th century made it possible to diagnose diseases earlier, before the patient showed clinical signs of having the disease. Technological advances in the coming century will make it possible to identify diseases at increasingly earlier stages. In certain cases, the diagnosis may occur before the disease process has begun, which increases the prospect of disease prevention.

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.10
Figure 19.10

Pharmacogenomics. Just as a prism subdivides visible light into separate wavelengths that are invisible to the human eye without the prism, the new molecular diagnostics reveal underlying, invisible genetic variation in groups of patients who appear uniform.

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.11
Figure 19.11

Pathogen identification. Monoclonal antibodies with fluorescent tags quickly confirm the presence of HSV in cultured cells. In this case, the monoclonal anitibodies are specific for HSV-2 infections and do not react with HSV-1- infected cells. (Photograph courtesy of Craig Lyeria, Centers for Disease Control and Prevention.)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.12
Figure 19.12

Assessing resistance to an antibiotic. These bacteria are growing on media that contains the antibiotic tetracycline. All of the strains, except the one that is circled, are resistant to tetracycline. (Photograph courtesy of Linda Bartlett, National Cancer Institute, National Institutes of Health.)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.13
Figure 19.13

Targeted therapy with monoclonal antibodies. Monoclonal antibodies can deliver chemotherapeutic toxins specifically to cancer cells. () The cytoplasm of tumor cells in breast tissue is stained brown with a monoclonal antibody that recognizes an antigen that occurs in cancer cells but is rare in normal, differentiated cells. () The same monoclonal antibody is able to locate a single breast cancer cell that has metastasized to the patient's liver. (Photographs courtesy of Jeffrey Schlom, National Cancer Institute, National Institutes of Health.)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.14
Figure 19.14

Taxol production. The anticancer drug taxol occurs in the bark of the Pacific yew tree. () The slow-growing yew tree reaches 5 feet in a number of decades. () It takes 30,000 pounds of bark to produce 1 kg of taxol. Between 2,000 and 4,000 trees had to be cut down to obtain that much bark. () Taxol is extracted from ground bark and purified. Plant cell culture provides another method for taxol production. (Photographs by Mike Trumball, Hauser Northwest, courtesy of National Institutes of Health.)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.15
Figure 19.15

Medicines from the ocean. Marine organisms, such as this sponge, are rich sources of potential therapeutic molecules. Like plants, many invertebrate organisms on coral reefs are sedentary and defend themselves with chemicals. (Photograph courtesy of the National Underwater Research Program, National Oceanic and Atmospheric Administration.)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.16
Figure 19.16

Treating cancer with immune system molecules. In this experiment, investigators injected mice with cancer cells. Within a few weeks, more than 250 tumors were evident in their lungs (left).The lungs on the right are from mice treated with interleukin-2, a protein normally secreted by the immune system, and a type of T cell. On average, the treated mice had fewer than 12 tumors. (Photograph courtesy of Steven Rosenberg, National Cancer Institute, National Institutes of Health.)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.17
Figure 19.17

Cancer and immune system cells. The immune system has a difficult time distinguishing cancer cells from normal cells because they are both “self.”Cancer vaccines teach the immune system to recognize the tumor as foreign. () A metastatic cancer cell (note the pseudopods). () Macrophages recognize the cancer cell and begin to stick to it. () Macrophages inject toxins into the cancer cell, which begins losing its pseudopods. () The macrophages fuse with the cancer cell, giving it a lumpy appearance. () The cancer cell shrinks up and dies. (Scanning electron micrographs courtesy of Raouf Guirgus and Susan Arnold, National Cancer Institute, National Institutes of Health.)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.18
Figure 19.18

Enzyme replacement therapy for Gaucher's disease. In 1991, Roscoe Brady of the National Institutes of Health isolated enough glucocerebrosidase from human placentas to give injections of the missing enzyme to 12 patients. Even though the injections had dramatic effects, isolating the enzyme from placental tissue was not cost-effective. Using recombinant DNA techniques, the gene that encoded the enzyme was engineered into yeast cells, making glucocerebrosidase replacement therapy a viable option. () Before. () After. (Photographs courtesy of Roscoe Brady, National Institute of Neurological Disorders and Stroke, National Institutes of Health.)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.19
Figure 19.19

Gene therapy. () Children with SCID, which can have a number of causes, must spend their lives in germ-free environments. () In 1991, two children with SCID received gene therapy to correct the genetic defect. (Photographs courtesy of National Institute of Allergy and Infectious Diseases, National Institutes of Health [A], and Michael Blaese,National Institutes of Health [B].)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.20
Figure 19.20

Gene replacement therapy. For genetic defects that affect cells derived from bone marrow stem cells, such as SCID, bone marrow is removed from the patient, and the stem cells are multiplied in cell culture. A correct copy of the gene is inserted into a viral vector, using recombinant DNA techniques. The virus is cultured with the bone marrow cells. It infects the cells and inserts the replacement gene into some of them. Radiation destroys the patient's defective bone marrow cells, and the physician injects cultured cells, now containing the correct gene, into empty bone marrow cavities. To date, only a few of the gene replacement trials have been therapeutic.

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.21
Figure 19.21

Stem cell proliferation. To maintain a constant supply of stem cells while continuing to provide differentiated cells for renewing tissue, a single stem cell divides into two daughter cells. One daughter differentiates, and one daughter remains a stem cell.

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.22
Figure 19.22

ES cell culture. To generate a culture of ES cells, researchers remove the inner cell mass from a blastocyst. Inner cell mass cells and their derivative ES cells have the potential to become any cell type. If placed into the uterus, however, neither will develop into a complete organism, because inner cell mass and ES cells cannot implant into the uterine wall. Trophoblast cells are required for implantation.

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.23
Figure 19.23

AS cell differentiation. Scientists are determining the unique culture conditions, necessary growth factors, and nutritional requirements that turn a specific type of adult progenitor stem cell into terminally differentiated cells. Note that cells have different levels of stemness in the differentiation process. Scientists are also studying the factors responsible for dedifferentiation and transdifferentiation.

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.24
Figure 19.24

Tissue engineering. () The small tissue construct uses cartilage stem cells, grown in culture, embedded in a biocompatible scaffolding material. When implanted into damaged bone, the construct stimulates the growth and differentiation of bone stem cells, which regenerate healthy bone. () Scientists are culturing stem cells to develop an implantable artificial pancreas that will regulate insulin for more than a year before needing to be replaced by a minor surgical procedure in hope of developing healthy pancreatic tissues for diabetics. (Photographs by Gary Meeks, courtesy of the Bioengineering Department, Georgia Institute of Technology [A], and courtesy of the Georgia Institute of Technology-Emory Center for Engineering Living Tissues [B].)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.25
Figure 19.25

Immune-compatible stem cells. To maximize the therapeutic potential of stem cells, the cells must not be seen as foreign by the immune system. This is best achieved by using the patient's own cells. In this example, the patient has a disease or injury that is repairable by neural stem cells, such as Parkinson's disease or a spinal cord injury. Nuclei removed from the patient's skin cells are implanted in a donated, enucleated egg. After the cells are cultured for approximately 4 to 5 days, a blastocyst is produced. The inner cell mass of the blastocyst is removed and cultured, creating a line of hES cells that are genetically identical (except for the mitochondrial DNA from the egg donor) to the patient. Treatment with appropriate differentiation factors converts the ES cells into neural stem cells and then into fully differentiated nerve cells. These are implanted in the patient in hope of replacing the diseased or injured cells with healthy nerve cells.

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.26
Figure 19.26

Vaccine production.To produce vaccines for viral diseases, the virus must be grown in living tissue. Typically, companies that manufacture vaccines use the embryos in chicken eggs. In this photograph, pockmarks in chick embryonic tissue indicate colonies of the smallpox virus. (Photograph courtesy of John Noble, Centers for Disease Control and Prevention.)

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Image of Figure 19.27
Figure 19.27

DNA vaccines and the immune response. Plasmids altered to carry a gene for a protein (antigen) produced by a pathogen are injected into muscle cells. The gene encoding the antigen is transcribed into mRNA, which moves to the ribosome, where it is translated into the antigen. The cell secretes some copies of the antigen and chops others into small pieces. Proteins that identify every cell in the body as self carry the antigen pieces to the cell surface. In response, the immune system synthesizes T cells that will recognize the pathogen's antigen, while the secreted antigens trigger the production of antibodies by the B cells of the immune system.

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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References

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Tables

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Table 19.1

Clinical chemistry

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Table 19.2

Simple genetic diseases

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19
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Table 19.3

Gene therapy trials for nongenetic diseases

Citation: Kreuzer H, Massey A. 2005. Health Care Applications, p 475-507. In Biology and Biotechnology. ASM Press, Washington, DC. doi: 10.1128/9781555816094.ch19

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