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The Challenge of Parasite Control
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Transgenesis refers to the deliberate introduction of exogenous genetic material into a living organism. The newly acquired genes, called transgenes, endow the recipient organism with new properties that will be transmitted to progeny. Such genetic engineering has increasingly been considered as a means of vector control. If vector capacity can be reduced with this technique, the hope is that transgenic vectors can be released into areas of endemicity, resulting in reduced transmission and morbidity. Such genetic methods, usually used in tandem with more conventional control, have been under investigation since the 1950s. The operational application of genetically altered vectors to reduce transmission has proven to be one of the most difficult challenges of vector control. Nevertheless, over the last two decades, there have been tremendous advances in the fields of vector genomics and proteomics and in the ability to genetically manipulate medically relevant vectors. Consequently, encouraging results in the laboratory are beginning to show promise in the field, and in some cases, the use of transgenic vectors to control disease transmission is already operational.
Herpesvirus microRNAs for Use in Gene Therapy Immune-Evasion Strategies
Published in Yashwant Pathak, Gene Delivery, 2022
Vineet Mahajan, Shruti Saptarshi, Yashwant Pathak
Targeted transfer of a therapeutic transgene is central to safe and effective gene therapeutic procedures.15 Currently, microRNA-dependent post-transcriptional suppression of transgene expression is an emerging new technology. Identification of viral miRNA as targets for treating viral diseases and associated cancers is also being explored. Several miRNA-targeted therapeutics are now in clinical development, prominent examples being a mimic of the tumor suppressor miRNA miR-34, which reached phase I clinical trials for treating cancer, and hepatitis therapeutic, antimiRs targeted at miR-122, in phase II trials.16 A significant barrier to miRNA-based therapy, however, is the development of targeted delivery paradigms with minimum toxicity. Recently, an engineered miRNA-based regulatory element was shown to control deleterious overexpression of a target gene in a Rett syndrome murine model.17 Another study reported miRNA-mediated transgene de-targeting to promote immune tolerance of a transgene-encoded antigen.4 Combination of the pleiotropic regulatory potential of miRNAs with gene therapy can allow targeted and potent expression of transgenes in specific tissue environments. Strategies for delivering miRNA therapeutics in a stable manner to target sites involve delivering miRNAs with synthetically modified oligoribonucleotides (ORNs) that mimic the native miRNA duplex or nanotechnology-based platforms.18
Methods of Evaluation in Orthopaedic Animal Research
Published in Yuehuei H. An, Richard J. Friedman, Animal Models in Orthopaedic Research, 2020
The basic terminology given here is adapted from the reviews by Shore and Kaplan.251,252 A gene is a unit of heredity, consisting of a segment of chromosomal DNA that is required for production of a functional protein or RNA. The gene contains both coding and regulatory regions. A transgene is a foreign gene which has been spliced into an animals original genomic DNA. mRNA is a type of RNA that contains protein coding information. Nucleotide sequence refers to the order of nucleotides in a given segment of DNA or RNA. Translocation is the transfer of a portion of DNA from one chromosome to another. A probe is a DNA or RNA molecule that is labeled, or tagged, and can then be used to locate a complementary DNA or RNA strand through hybridization. Vectors are DNA molecules that are used as carrier molecules for cloned DNA sequences. They contain information which allows recombinant molecules to be replicated in host bacterial cells. A plasmid is a small circular double-stranded DNA molecule which is found in bacteria and replicates independently of the host chromosome. They are commonly used as vectors in molecular cloning. A recombinant DNA molecule is a DNA molecule containing segments of DNA from different origins, such as a piece of human DNA that has been joined to a plasmid DNA. A clone is a term used to describe identical segmental DNA molecules produced by recombinant DNA technique. Molecular cloning is a process by which a specific segment of DNA is isolated and then numerous identical copies, or clones, of that segment of DNA are generated.
Locked and loaded: engineering and arming oncolytic adenoviruses to enhance anti-tumor immune responses
Published in Expert Opinion on Biological Therapy, 2022
Replacing a viral ORF with a transgene ORF utilizes the intrinsic viral expression program to express transgenes. It can make transgenes express as if they were early, intermediate, or late genes for programmed expression. It also entrains transgene expression into the viral program such that if the viral genes are not activated, the transgenes might not be expressed. This ORF substitution strategy has advantages in minimizing transgene cassette space over other approaches that require external regulatory sequence elements. As we reviewed, E1B and E3 genes are non-essential for viral replication and virion production, thus making those genes potential candidates for replacement with therapeutic transgenes. Terry Hermistons group has shown that E3-CR1-α(6.7 K)/gp19K, E3-ADP, and E3-RID-α/β/E3-14.7 K regions can be replaced by a transgene or multiple transgenes (Figure 2) [70–73]. Reporter and IFN genes also have been inserted in E3B regions [74]. Notably, the choice of exact insertion sites in the complex E3 region can affect neighboring E3 ORFs expression and the overall viral fitness [72]. This approach can save some space; however, human Ads do not replicate well in most mouse cells and other animal cells. Therefore, transgene cassettes that piggyback their expression on Ads’ transcripts will probably not be expressed well in some animal models of cancer.
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].
How necessary are animal models for modern drug discovery?
Published in Expert Opinion on Drug Discovery, 2021
Transgenic animals have a foreign gene introduced into their genome. Such animals are usually produced by DNA microinjection into the pronuclei of a fertilized egg that is subsequently implanted into the oviduct of the surrogate mother. Transgenic animals have become a key tool in functional genomics in order to generate models for human diseases and validate new drugs [20]. Transgenesis includes the addition of foreign genetic information to animals and specific inhibition of endogenous gene expression. The knockout animals are transgenic that have a specific interest gene disabled are transgenic, and are widely used to investigate both normal gene function, as well as the analyses of patho-biological roles of select genes involved in various disease states [21]. In addition, such transgene/knockout animal models are actively used in the development of new therapeutics and associated strategies.