Abstract:
:We used Cre/loxP recombination to swap targeting ligands present on the adenoviral capsid protein IX (pIX). A loxP-flanked sequence encoding poly-lysine (pK-binds heparan sulfate proteoglycans) was engineered onto the 3'-terminus of pIX, and the resulting fusion protein allowed for routine virus propagation. Growth of this virus on Cre-expressing cells removed the pK coding sequence, generating virus that could only infect through alternative ligands, such as a tyrosine kinase receptor A (TrkA)-binding motif engineered into the capsid fibre protein for enhanced infection of neuronal cells. We used a similar approach to swap the pK motif on pIX for a sequence encoding a single-domain antibody directed towards CD66c for targeted infection of cancer cells; Cre-mediated removal of the pK-coding sequence simultaneously placed the single-domain antibody coding sequence in frame with pIX. Thus, we have developed a simple method to propagate virus lacking native viral tropism but containing cell-specific binding ligands.
journal_name
Virologyjournal_title
Virologyauthors
Poulin KL,Tong G,Vorobyova O,Pool M,Kothary R,Parks RJdoi
10.1016/j.virol.2011.09.004subject
Has Abstractpub_date
2011-11-25 00:00:00pages
146-55issue
2eissn
0042-6822issn
1096-0341pii
S0042-6822(11)00407-7journal_volume
420pub_type
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