Study of the exosomes: RNA composition of exosomes as potential biomarkers for cancer; Exosomes as a delivery vehicle for therapeutic shRNAs
Exosomes are membrane microvesicles that are secreted by many cell types and the tumour cells are thought to generate a larger number of such vesicles. Exosomes contain a large set of the specific RNAs, both mRNAs and microRNAs, which can be delivered into the recipient cells via fusion of the exosome and cellular membranes. The foreign mRNAs can then be translated and the microRNAs can potentially regulate gene expression of the host cell. Thus, exosomes can be considered as the vehicles for transferring genetic information from one cell to another. In this respect, exosomes are likely to be especially employed by the tumour cells to invade the surrounding normal cells with the RNAs which will then deregulate gene expression of the recipient cells making them working in support of the tumour cells.
The first aim is to identify the specific RNA molecules extracted from the exosomes that are released from the tumour cells which can be potentially used for diagnostic or prognosis of certain types of cancer. The exosomes will by purified from the media of cultured cells and their RNA content will be analysed by microarrays, RNA cloning/sequencing and quantitative RT-PCR. The second aim is to investigate whether the shRNAs inducibly expressed in the genetically engineered human cell lines could be delivered to the recipient cells via exosomes and can cause the functional knockout of the specific gene by a cognate shRNA. The cell lines expressing inducible shRNAs will be generated; the exosomes will be purified from these cells and used to treat the host cells. It is anticipated that the exosomes from the shRNA expressing cells will knock down the corresponding gene causing death of the malignant cells.
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This is a self funded topic
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