Production of Young Red Blood Cells to Support Drug and Vaccine Development against Plasmodium viva Malaria

Technology Overview

Plasmodium vivax is the most geographically widely distributed human malaria parasitecausing stately morbidity and severity in affected populations. In vitro continuous culture of P. vivax is lacking thus causing the slow progress on vaccines/drugs development compared withP. falciparum. The major limitation for the establishment of in vitro culture of P. vivax is its preference to invade and develop in young red cells thus there is a need for the continuous supply of reticulocyte. Until now, little is known about the characteristics ofhost cells which could support the propagation of the parasite.Based on the recently developed hESC/iPS technology which will expedite the advances of in vitro culture of P. vivax, as well as the abilities of hESC/iPS for being able to be immortally propagated, differentiated into reticulocyte and easily manipulated, we aim to obtain a scalable source of reticulocytes for in vitro culture of P. vivax. Thisin vitro continuous lines of P. vivax will be an invaluable resource for the research community and will help advancethe vaccine and drug development for malaria.

Technology Features & Specifications

Cultivation of hESC/iPS-derived erythroid lineage Published differentiation protocolsfor hESC/iPSC progenitors were modified for optimized cell differentiation conditions and large scale production of the target cells. With this technology,hESC/iPSC progenitors aredifferentiated to the erythroid lineage with the reticulocyte-likecells obtained successfully used for P. falciparum culture. This technology helps in overcoming current challenges of obtaining young red blood cells from normal blood donor due to the inherent nature of the body's ability to of producing young red blood cells as intermediates of the process of red blood cell production. Establishment of in vitro continuous culture of P. vivax to support drugs and vaccinesdevelopment Furthermore, this technology allows for the easy identification of the phenotype forhESC/iPS-derived erythroid lineage targeted by P. vivax parasites. Hence,the production of thosetarget cells can be scaled-up and used for the supply ofP. vivax continuous culture with applications in the development of new drugs and vaccines against P. vivax.

Potential Applications

Building on the recent advances of hESC/iPSC cell technology and under optimal cell differentiation conditions, this technology allows for the immortalpropagationand differentiationto the erythroid lineage with high yields. Moreover, the morphology of these cells have shown to have similar red blood cell specific surface markers like CD235a. Hence, themass production of the host cell allows for the production of a source of high yield and high quality reticulocyte-like cells to be used as a continuous supply for in vitro culture of P. vivax. The in vitro continuous culture of P. vivax will be an invaluable tool inenabling vaccines and drugs development against this wildly distributed parasite.

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