Sustained multilineage gene persistence and expression in dogs transplanted with CD34+ marrow cells transduced by RD114-pseudotype oncoretrovirus vectors

Surface-engineering of lentiviral vectors

“…These results may reflect differences in the pattern of receptor expression on the CD34 + cells for the different glycoproteins and seem to contradict those previously reported with oncoretroviral vectors [34]. However, in agreement with the previous studies [34,61,62], the combined use of the RD114/TR glycoprotein and retronectin, a fibronectin recombinant fragment that stimulates infection, strongly increased transduction of human CD34 + cells, allowing RD114/TR-pseudotyped lentiviral vectors to surpass those pseudotyped with VSV-G. The mechanisms by which the retronectin fragment enhances infection may involve the co-localisation of retroviral particles and target cells [63], although alternative explanations, involving inhibition of apoptosis and stimulation of cell division, have been proposed [64].…”

“…Transduced cells could repopulate NOD/ SCID mice and dogs with an efficiency similar to that of non-transduced cells and displayed multilineage expression [34,61,62]. From these studies, it was suggested that, in human CD34 + cells, the ''major barrier to gene transfer is at the receptor level and is not due to the quiescence of the target cells'' [34].…”

“…Recent reports have demonstrated that onco-retroviral vectors pseudotyped with the RD114 glycoprotein efficiently transduce human and canine CD34 + cells [34,45,61,62]. Transduced cells could repopulate NOD/ SCID mice and dogs with an efficiency similar to that of non-transduced cells and displayed multilineage expression [34,61,62].…”

“…Alternatively, these results may not necessarily involve differences in receptor density and/or initial virus/receptor interaction parameters. Several reports have shown that transduction efficiency does not correlate with the level of receptor expression [62,65] but rather establishes the importance of post-binding events such as receptor clustering, membrane fusion mechanism, site of fusion, uncoating and migration of the viral particle from the site of uncoating and the nucleus [66,67].…”

Improved transduction of human sheep repopulating cells by retrovirus vectors pseudotyped with feline leukemia virus type C or RD114 envelopes

“…Recombinant retrovirus vectors with envelopes derived from the RD114 virus have been used successfully to transduce primitive human, canine, and primate hematopoietic cells, often at high levels. [40][41][42][43][44][45] Feline leukemia virus type C (FeLV-C) causes redcell aplasia in cats. The FeLV-C envelope recognizes a heme transporter protein (FeLV-C receptor [FLVCR]).…”