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A New Era of Transgenics in Parasitic Nematodes

One of the most commonly known nematodes in the scientific community is Caenorhabditis elegans. Ever since Sydney Brenner introduced it as a model organism to study nervous system, the use of C. elegans in various disciplines of biological research has yielded significant results pertinent to the understanding of cell biology, genetics, developmental biology, and neurobiology. The genetic tools developed in C. elegans, like RNA interference, have been successfully utilized in other model organisms and have dramatically changed our understanding of genetic pathways and gene function.

A rather lesser known but significantly important group of nematodes are the parasitic nematodes. Parasitic nematodes cause major financial and socioeconomic burden to the modern society. More than one-tenth of the human population is estimated to be infected with parasitic nematodes. Parasitic nematodes are also a major concern to the livestock industry with a loss in value of hundreds of millions of dollars. There has been limited progress in controlling parasitic nematodes with only a few anthelmintic drugs available in the market. Furthermore, development of resistance to the available drugs creates a major hindrance in the treatment of these parasitic nematodes.  

While several researchers have tried to adapt the knowledge from the genetic tools available in C. elegans to study host-parasitic interactions, the success has been limited. This is probably because of the large diversity present in the of the phylum nematode. The nematodes not only vary in size and the food they eat, but they also differ in the internal morphology.

After working in C. elegans transgenics for more than four years, I was fascinated when I got the opportunity to work on transgenics in parasitic nematodes. I have worked with two parasitic nematodes to develop transgenic tools. An insect parasite Heterorhabditis bacteriophora and a vertebrate parasite, Ancylostoma that infects cats, dogs, hamsters, and humans. The challenge in working with nematodes other than C. elegans became clear to me when I studied these parasitic nematodes in detail. The advantage of performing genetics in hermaphroditic C. elegans is lost in most of the commonly occurring parasitic nematodes that have distinct males and females in the life cycle. This is further complicated by the presence of an obligatory host that is required for the development of the larvae to adult and by the morphological diversity observed in the gonads of these nematodes.

However, CRISPR/Cas9 has revolutionized the field of genome editing and transgenesis and recently several researchers working on parasitic nematodes have successfully utilized the technology. The technology uses a guide RNA and a Cas9 protein to target a specific region of the genome that can be nicked. Larger fragments of DNA can be introduced at the cut site resulting in the integration of the foreign gene fragment. The fascinating feature of the approach is the precision of the DNA fragment insertion due to its dependence on native DNA sequence.  Delivery of CRISPR/Cas9 components is also not limited to traditional microinjection technique. The components can be delivered using other means like carrier molecules (lipofectamine) or virus like lentivirus.

I believe that this is a fascinating period in the field of transgenics and gene editing in parasitic nematodes and soon we will be moving quickly towards successful control of parasitic nematodes.

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About The Author

Ramesh Ratnappan

Ramesh is a scientist at NemaMetrix, working with the molecular biology team. He specializes in transgenics in C. elegans and parasitic nematodes, Heterorhabditis (insect parasite) and Ancylostoma (hookworm). He finished his Ph.D. from the University of Iowa and worked at the University of Pittsburgh and George Washington University for his postdoctoral training. He is interested in expanding the techniques standardized in C. elegans to parasitic nematodes.

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