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Concentration of viral vectors by co-precipitation with calcium phosphate

✍ Scribed by Linh Pham; Hong Ye; Francois-Loic Cosset; Stephen J. Russell; Kah-Whye Peng


Publisher
John Wiley and Sons
Year
2001
Tongue
English
Weight
161 KB
Volume
3
Category
Article
ISSN
1099-498X

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✦ Synopsis


Background:

The envelope glycoproteins, surface unit (su) and transmembrane (tm) of the murine leukemia virus (mlv) are not covalently linked and tend to dissociate upon high-speed centrifugation, leading to loss of vector infectivity. this study describes a gentle and simple method to concentrate mlv vectors or hiv vectors pseudotyped with mlv envelopes. having a fast and inexpensive method to concentrate large volumes of vector supernatant will facilitate in vivo experiments and clinical trials that require high titer vector stocks.

Methods:

The methods employed in the study were co-precipitation of viral supernatant with calcium phosphate, low-speed centrifugation, dialysis, and infection assays with lac-z transducing vectors.

Results:

Murine leukemia virus vectors and hiv vectors pseudotyped with vesicular stomatitis virus glycoprotein (vsv.g) or mlv envelopes were concentrated successfully using the calcium phosphate co-precipitation method. parameters that influence virus yield and the reproducibility of the method were investigated. the optimized protocol involves virus harvest in serum-free media, co-precipitation using 60mm calcium chloride, pelleting at 2,000 g, resuspending the pellet in a small volume of 0.1m edta-saline, and dialysis against saline to remove edta. volumes were decreased from 300 ml to 10 ml, with 50-100% recovery, and titers can be concentrated up to 1,000-fold.

Conclusions:

The calcium phosphate co-precipitation method to concentrate virus is applicable to retrovirus and lentivirus preparations. it uses simple techniques and does not require expensive equipment. multiple rounds of co-precipitation can be carried out if required.