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Applications for Drug Development
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Jessica Kalra, Donald T. Yapp, Murray Webb, Marcel B. Bally
Animal models have been used since the 1950s to study tumors in situ, whether examining basic biological concepts of cancer development or therapeutic response. Over the past six decades, the diversity of models used in oncology research has increased, from cell lines injected into animals, animals with reporting systems that can assess biological function, to transgenic organisms that develop spontaneous disease. In each case, small animal imaging can play roles in monitoring disease progression, localizing disease, and evaluating changes in pathology as a result of intervention in the same animal over time.
Prion controversy, 1982–1997
Published in Kiheung Kim, The Social Construction of Disease, 2006
Meanwhile, Prusiner's lab in San Francisco launched an ambitious series of experiments adopting yet another set of new experimental techniques from the cutting edge of molecular biology, namely the construction of transgenic organisms, which Prusiner intended to further elucidate the role of PrP and its gene in scrapie and other diseases. The project was led by a Scottish molecular biologist, Mike Scott, and a new postdoctoral researcher, Karen Hsiao. During his search for the hamster PrP gene, Prusiner's team had developed techniques for cloning the cDNA complementary to that gene. It was a small step to being able to produce and clone the gene itself. Moreover, techniques had recently become available for inserting such cloned genes into the embryos of various organisms, including mice.3 Consequently, Prusiner's team was now able to create a strain of transgenic mice that carried the hamster PrP gene.4 The transgenic mice were created by injecting the PrP gene into the male pronucleus of a fertilised mouse egg. The injected eggs were then transferred into pseudopregnant mice. According to Jean Manson and Nadia Tuzi, ‘this approach generates transgenic mice in which the transgene is integrated randomly into the murine genome. Although the expression level and distribution of PrP cannot be controlled with this transgenic approach, its use has yielded many interesting and informative TSE models’ (Manson and Tuzi 2001: 3).
The Challenge of Parasite Control
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
The use of transgenic vectors is not without important problems. Any reduction strategy, for instance, requires regular and repeated introduction of the transgenic organism to ensure sustained control. Furthermore, genetically modified vectors are frequently at a competitive disadvantage as compared to their wild-type conspecifics. The genetic manipulation itself often renders transgenic vectors less fit than more vector-competent and robust wild-type vectors. Consequently, some of the same issues that plague more conventional control efforts, such as the need for regular reintroduction and sustained effort, are relevant for modified vectors as well. One strategy to help overcome the potential reduced fitness of transgenic vectors would be the use of paratransgenesis: the genetic manipulation of the vector’s microbiota rather than the vector itself. To cite just one example, Asaia bogorensis, a vertically transmitted bacterium found in the digestive tract and reproductive organs of Anopheles mosquitoes, has been genetically modified to express a protein called scorpine, derived from scorpion venom. The transgene is accompanied by promoters that are activated by nutrients found in a mosquito’s blood meal. Thus, scorpine is only produced immediately following a blood meal, which reduces or eliminates any fitness cost on the mosquito. Scorpine prevents the development of the Plasmodium ookinete stage within the mosquito (see Figure 2, Page 525 in the Rogues’ Gallery). Not only do such mosquitoes fail to produce the sporozoites infective to humans, but because the bacterium is vertically transmitted, it is able to spread through the mosquito population. Other issues relate to potential environmental problems that may result from the introduction of transgenic organisms. The unintended or unanticipated effects of such an introduction are largely unknown.
The relevance of studying insect–nematode interactions for human disease
Published in Pathogens and Global Health, 2022
Zorada Swart, Tuan A. Duong, Brenda D. Wingfield, Alisa Postma, Bernard Slippers
With an increasing number of insect genomes being sequenced and made available in public databases, together with the development of advanced gene-editing tools, gene modification provides an alternative to traditional chemical or environmental vector control measures [51,52]. Genetically modified mosquitoes are already being released to control mosquito populations responsible for the spread of dengue fever, for example [53,54]. Releasing transgenic organisms is of course not without risks. Modified genes might be transmitted to the wild-type population and changes in the wild-type population could affect the virulence of the vector-borne pathogen. Molecular insight into the interactions between parasites, vectors, and bacterial symbionts is therefore important not only to discover additional treatment targets but also to ensure the safety of existing and developing control measures [55].