Unit:
Τομέας Βιοχημείας Μοριακής ΒιολογίαςLibrary of the School of Science
Dissertation committee:
Τσιτήλου Σόνια Αναπλ. Καθηγ.(Επιβλέπουσα), Βασιλακοπούλου Διδώ Αναπλ. Καθηγ., Βασιλόπουλος Γεώργιος Επικ. Καθηγ.
Original Title:
Μελέτη της δράσης φορέων τύπου spuma που εκφράζουν anti-α σφαιρίνης shRNA (short hairpin RNA) και β-σφαιρίνη σε πειραματικά μοντέλα θαλασσαιμίας
Summary:
Therapeutic β-globin vectors have been constructed and tested for over two
decades as an alternative treatment options for β-thalassemia. In order to test
the efficiency of β-globin expression from our FV vectors we transduced cells
of the MEL line, primary hematopoietic progenitors from a thalassemic mouse
model as well as from human β-thalassemia patients. We demonstrate that while
both FV vectors can produce human β-globin at levels that can ameliorate the
ineffective erythropoiesis seen in thalassemic cells, the HS40 element is
marginally more efficient than the combination of HS2/HS3, both ex vivo in
murine HSCs and human CD34+ cells, as well as in the mouse model of β-
thalassemia. Given the compact size of the HS40 element, we propose that it can
be used alternatively to the LCR sequences for regulated β-globin expression in
gene therapy approaches with FV vectors. Another goal of this study is to
create FV vectors that co-express the β-globin gene alongside with a short
hairpin RNA against the α-globin gene in order to achieve a more efficient
restoration of the β- to α-globin imbalance. The result was that the combined
FV vector achieved more efficient restoration of the distorted erythropoiesis
observed in thalassemic cells and in comparison to the single vectors.
Keywords:
Gene Therapy, β-Thalassemia, β-Globin, Foamy Viral Vectors, RNA Interference
Number of index pages:
3-6
Number of references:
194
