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Identifier

000426483

Title

Design of engineered exosomes as a drug delivery system

Alternative Title

Σχεδιασμός εξωσωμάτων με σκοπό τη χρήση τους ως φορείς φαρμάκων

Thesis advisor

Γαρίνης, Γιώργος

Abstract

Cells have evolved a battery of overlapping DNA repair pathways to keep their genome intact and transmit it faithfully to progeny. Nucleotide Excision Repair (NER) is a highly conserved DNA repair mechanism that cells employ to repair UV-induced DNA lesions. Defects in NER lead to enhanced cancer predisposition or to a heterogeneous group of progeroid and developmental disorders. Besides genome maintenance, multicellular organisms employ adaptive and innate immune responses to guard themselves against foreign pathogens and threats. Recent evidence points to reciprocal interactions between DNA repair mechanisms, DNA damage responses and immunity. Here, we present evidence that irreparable DNA damage in distinct cell types triggers the accumulation of double- (ds.) or single-strand (ss.) DNA moieties in the cytoplasm. In turn, ds. or ss. DNA species lead to the activation of pro-inflammatory signaling associated with a type 1 interferon response. Based on these findings, we propose a therapeutic strategy allowing us to generate engineered exosomes that will carry a nuclease that will be targeted to specific cell types. The latter strategy allows the rapid elimination of cytoplasmic DNA moieties, thereby substantially reducing chronic inflammation.

Language

English

Subject

DNA damage

ERCC1

Interferons

Nucleases

Βλάβη γενετικού υλικού

Εξωσώματα

Νουκλεάσες

Issue date

2019-11-29