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Reprogramming by Virus

Reprogramming by Virus
Retro-and lentivirus: Retro- and lentiviral delivery vectors have been used to generate iPSCs almost every lab, because this viral transduction is easily implemented in most biomedical research labs. Using this delivery system, the reprogramming efficiency was 0.01–0.02% in human cells with iPSC colonies occurring between 25 and 30 days post-infection. As retroviruses only infect dividing cells, lentiviral delivery system was more popular so that both dividing and non-dividing cells could be infected in the hopes of improving reprogramming efficiency.
Lentiviral plus cre-lox mediated transgene excision: To date, the first production of transgene free iPSCs were performed with lentiviral vectors containing loxP sites in the 5′and 3′LTR of the viral vectors. The existence of loxP sites gave a substrate to remove most of the transgene sequences by Cre-mediated recombination.
Adenovirus: Adenovirus is a non-integrating virus that does not infect replicating cells. The first known research reporting the production of iPSCs with an adenoviral vector was reprogrammed mouse tail tip fibroblasts to iPSCs. However, the reprogramming efficiency was in the range of 0.001–0.0001%, because the expression window of reprogramming factors is too narrow to induce the expression of endogenous factors required to transition somatic cells.

CNS drug discovery

CNS drug discovery has been hampered by inadequate understanding or consideration of a number of factors. These include the complexity of brain anatomy and function; the neuro-PK with regard to the blood-brain barrier (BBB) transport and intra-brain distribution as well as the measures to study these processes; adequate biomarkers of CNS drug effects (neuro-PD), and the complex nature of CNS diseases. Also, the reductionist view and thereby lack of understanding of the interaction and interdependencies of all these factors have contributed to the high attrition rates of CNS drugs.

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