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Antibody drug conjugates are an exciting therapeutic modality that combines the targeting specificity of antibodies with potent cytotoxins to selectively kill cancer cells. The targeting component improves efficacy and protects non-target cells from the harmful effects of the payload. To date 15 ADCs have been approved by regulatory agencies for commercial use and shown to be valuable tools in the treatment of cancer. The assembly of an ADC requires the chemical ligation of a linker-payload to an antibody. Conventional conjugation methods targeting accessible lysines and cysteines have produced all the ADCs currently on the market. While successful, technologies aiming to improve the homogeneity and stability of ADCs are being developed and tested. Here we provide a review of developing methods for ADC construction. These include enzymatic methods, oligosaccharide remodelling, and technologies using genetic code expansion techniques. The virtues and limitations of each technology are discussed. Emerging conjugation technologies are being applied to produce new formats of ADCs with enhanced functionality including bispecific ADCs, dual-payload ADCs, and nanoparticles for targeted drug delivery. The benefits of these novel formats are highlighted. [ABSTRACT FROM AUTHOR]

The development of genetically engineered resistance to plant viruses is a result of efforts to understand the plant-virus interactions involved in "crossprotection," a phenomenon observed with several plant virus diseases. Historically, expression of the coat protein gene of Tobacco mosaic virus in transgenic tobacco (Nicotiana tabacum) plants is the first example of transgene-mediated resistance to a plant virus. Subsequently, virus-derived sequences of several plant viruses were shown to confer virus resistance in experimental and/or natural hosts. For plant RNA viruses, virus complementary DNA sequences shown to confer resistance include wild-type genes, mutated genes that produced truncated protein products, and nontranslatable sense or antisense transcripts to various regions of the virus genome. Resistance also has been demonstrated for some viruses by mutant trans-dominant gene products, derived from the movement protein and replication-associated protein genes. In addition to virus-derived sequences, gene sequences of plant origin have also been used for transgenic resistance, and such resistance can be virus-specific, for instance, R genes isolated from resistant plant genotypes, or nonspecific, for example, ribosome inactivating proteins and proteinase inhibitors. Plantibodies and 2-5A synthetase, a class of proteins of mammalian origin, have also been useful in engineering plant virus resistance. In the case of transgenic resistance mediated by viral coat protein, the mechanism of resistance was suggested to operate during the early events of virus infection. However, transgene-mediated RNA silencing and generation of small interfering RNAs appears to be the primary mechanism that confers resistance to plant viruses. Despite the advantages of transgene-mediated resistance, current interest in the development and use of transgenic virus resistant plants is low in most parts of the world. However, because of its real potential, we believe that this technology will have more widespread and renewed interest in the near future.