An improved self-deleting retroviral vector derived from avian leukemia and sarcoma virus.
We have previously developed a self-deleting avian leukosis and sarcoma virus (ALSV)- based retroviral vector carrying an additional attachment (att) sequence. Resulting proviruses underwent deletion of viral sequences and were flanked either by two LTRs (LTRs proviruses) or by the additional att sequence and the 3' LTR (att proviruses). Herein, we have tried to increase (1) the self-deleting properties of this vector, either by raising the selection pressure applied on target cells or by optimizing the size of the internal att sequence, (2) the titer of the vector by deleting or inverting some viral sequences. Moreover, a new type of provirus flanked by att sequences at each end was isolated. Finally, under specific conditions, 100% of proviruses had internal sequences deleted, and as many as 92-100% of proviruses were no longer mobilizable by a replication-competent virus. The inactivation procedure achieved here might improve the biosafety of retroviral vectors.
Torne-Celer
Caroline
C
Université de Lyon, Lyon, France.
Moreau
Karen
K
Faure
Claudine
C
Verdier
Gérard
G
Ronfort
Corinne
C
D001355:Alpharetrovirus / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D011533:Proviruses / Q000235:genetics; D011784:Quail; D017384:Sequence Deletion / Q000235:genetics*; D016662:Virus Integration / Q000235:genetics*