Numerous experiments showed that a transgene is generally poorly expressed when it contains a cDNA rather than the corresponding genomic DNA; when it is integrated as multiple copies; when it contains non mammalian DNA sequences, namely CpG- rich sequences; and when it is integrated in a silent region of chromatin. The last phenomenon is known as position effect.Vector constructions may be performed taking these observations into account. It is now acknowledged that groups of genes, acting or not acting in a coordinated manner, are bordered by DNA sequences that insulate them from the rest of the chromosome. These sequences have been named insulators or LCRs (locus control regions). Insulators are composed of multiple elements. The inclusion of insulators in gene constructs greatly enhances the transgene expression.