Vol 45(2011) N 6 p. 857-871;
E.S. Knyazhanskaya1*, O.V. Kondrashina2, M.B. Gottikh1
Approaches to Site-Directed DNA Integration Based on Transposases and Retroviral Integrases1Belozersky Institute of Physical and Chemical Biology, Moscow State University, Moscow, 119899 Russia
2Department of Chemistry, Moscow State University, Moscow, 119992 Russia
Received - 2011-04-04; Accepted - 2011-05-10
The ability of retroviruses and transposons to insert their genome into the host cell makes them attractive objects for constructing gene therapy vectors. However, enzymes that insert genetic material do not possess any selectivity relative to target nucleotide sequences, which results in almost random DNA insertion into the recipient cell genome. This leads to mutations that in turn may cause certain undesirable consequences and sometimes neoplastic cell transformation. For successful functioning, it is a primary necessity to modify a retrovirus and transposon based genetic therapy systems in such a way that the directed vector integration into a target sequence in the human genome can be achieved. In this review, the approaches to date that have been developed for highly specific modification of the genome using fusion protein construction based on retroviral integrases and transposases are discussed, as well as cellular factors interacting with these enzymes.
integrase, transposase, directed integration, site-directed transposition