HIGH EFFICIENCY RETROVIRAL VECTORS THAT CONTAIN NONE OF VIRAL CODING SEQUENCES

摘要

The present inventionrelates to improved retroviralvectors for gene therapy. In thisinvention, retroviral vectors withhigher safety and efficiency areconstructed from MLV-basedstarting vectors, MON and MIN.The improved vectors havefollowing features: 1) sequencescorresponding to MLV-derivedpol gene are completelydeleted in the vectors, avoidinghomologous recombination whichhas been a baffling problem inconventional retroviral vectors,2) a heterologous intron, splicingacceptor and/or non-codingsequence are/is inserted intothe upstream position of cloningsite, maximizing the expressionof a foreign gene throughefficient splicing, 3) the vectorscontain either the full-lengthU3 sequence of 5' LTR or astrong heterologous promoterinstead, permitting the abundantproduction of RNA, 4) eitherIRES (Internal Ribosomal EntrySite) or internal SV40 minimalpromoter is inserted into the downstream position of cloning site, enabling the simultaneous expression of two or more foreign genes.Since the improved retroviral vectors of this invention turn out to be safe and to express the foreign gene efficiently, they are useful forgene therapy and the like.