Abstract:
:Serum-induced inactivation of retroviruses is the most critical limitation for in vivo gene transfer therapy. To solve this problem, we searched for reagents that protect retroviruses from inactivation. The effects of the protease inhibitors FOY-007 and FOY-305 and of an inhibitor of the complement pathway FUT-175, all of which have been used clinically, were investigated. All of these agents protected against the inactivation of retroviruses by human serum, with 1 microM FUT-175 providing the most effective protection. Thus, the co-administration of FUT-175 with retroviruses may make retrovirus-mediated in vivo gene transfer feasible for the treatment of patients. FUT-175 dose-dependently inhibited the classical pathway of complement in a hemolysis protection assay of sensitized sheep erythrocytes with guinea pig serum or by cell-lysis assay of mouse fibroblasts with human serum. However, increasing the FUT-175 concentration by 10-fold (10 microM) did not produce further protection against retroviral inactivation in most human sera. There was also no correlation between the serum-induced inactivation of retroviruses and either the amount of anti-alpha-galactosyl (anti-alpha-Gal) antibody or the complement activity in human serum. These results suggest that retroviruses are not inactivated by utilizing the same pathway leading to cell lysis by the classical complement system.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Miyao Y,Ikenaka K,Kishima H,Tamura M,Nakamura K,Kurumi M,Hayakawa T,Shimizu Kdoi
10.1089/hum.1997.8.13-1575subject
Has Abstractpub_date
1997-09-01 00:00:00pages
1575-83issue
13eissn
1043-0342issn
1557-7422journal_volume
8pub_type
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pub_type: 临床试验,杂志文章
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pub_type: 杂志文章,评审
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