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Protection of MLV vector particles from human complement
S Breun1, B Salmons, W H Günzburg
1Institute of Virology, University of Veterinary Sciences, Veterinärplatz 1, Vienna, A-1210, Austria.
Abstract:
Murine cell-derived MLV vector particles usually are highly sensitive to human complement-mediated lysis. Expression of the human complement inhibitor CD59 on murine packaging cells resulted in partial protection of these cells from lysis caused by human complement proteins. Furthermore, CD59 was incorporated into MLV vector particles released by these packaging cells, leading to an improved resistance of the virions against human complement-mediated inactivation.
Insights
Murine leukemia virus (MLV) vectors are vulnerable to human complement. Expressing CD59 on packaging cells protected them and improved MLV vector resistance to complement-mediated inactivation.
Area of Science:
- Biotechnology
- Immunology
- Virology
Background:
- Murine cell-derived Moloney murine leukemia virus (MLV) vector particles are typically susceptible to lysis mediated by the human complement system.
- The human complement system poses a significant challenge for the in vivo application of MLV vectors.
Purpose of the Study:
- To investigate the protective effect of expressing the human complement inhibitor CD59 on murine packaging cells.
- To determine if CD59 incorporation into MLV vector particles enhances their resistance to human complement.
Main Methods:
- Murine packaging cells were engineered to express human CD59.
- The susceptibility of CD59-expressing cells and the resulting MLV vector particles to human complement-mediated lysis was assessed.
Main Results:
- Expression of CD59 on murine packaging cells conferred partial protection against human complement-mediated lysis.
- CD59 was successfully incorporated into MLV vector particles produced by these cells.
- The resulting CD59-containing MLV vector particles exhibited enhanced resistance to inactivation by human complement.
Conclusions:
- Engineering murine packaging cells to express CD59 can partially protect the cells from complement lysis.
- Incorporation of CD59 into MLV vectors improves their resistance to human complement-mediated inactivation, potentially enhancing their therapeutic applicability.