Abstract
Extracellular vesicles have become a research focus for their potential as therapeutic vehicles that carry cargo substances. Extracellular vesicles may origin from the endosomal compartment and share several characteristics with the envelope of lentiviruses. A previous study reported that constitutive expression of the tetraspanin CD9, an extracellular vesicle marker, not only increases vesicle secretion from cells, but has also a positive effect on lentiviral transduction efficiency. Moreover, it was shown that expression of CD9 on the viral envelope in absence of viral glycoproteins was sufficient for the transduction of mammalian cells. In this study, we investigate the effect of CD9 and folate receptor alpha, a GPI-anchored protein, on biosynthesis and transduction efficiency of vesicles carrying lentiviral vectors. We demonstrate that neither CD9 nor FRα nor the combination of both were able to mediate a significant transduction of therapeutic vesicles carrying lentiviral RNA. Further studies are required to identify endogenous mammalian proteins that can be used for pseudotyping of viral envelopes to improve viral targeting without inducing immune responses.
Highlights
Extracellular vesicles (EVs) are defined as “particles naturally released from the cell that are delimited by a lipid bilayer and cannot replicate” [1]
CD9 expression was tested with qPCR and Western Blot (WB). qPCR results indicate a ΔΔCq of -8.82±0.32 s.d. for the CD9+ line and -9.17±0.15 s.d. for the GFP-CD9+ line compared to the average of the wild-type HEK 293 (WT) samples (0± 0.02 s.d.), equivalent to a change in expression of 459.33 and 576.44 times respectively (Fig 1A). p was
Our study aimed to identify mammalian proteins that are able to mediate transduction of lentiviral particles when expressed in the viral envelope
Summary
Extracellular vesicles (EVs) are defined as “particles naturally released from the cell that are delimited by a lipid bilayer and cannot replicate” [1]. They can be of endosomal origin (traditionally called “exosomes” [2]) or plasma-membrane derived (“ectosomes”) [3]. Exosomes share several characteristics with lentiviral particles: they both have a lipid bilayer membrane, they are similar in size and density [5, 6] and they carry nucleic acids such as RNA [7]. ESCRT, Alix and TSG101 are all involved in virus budding [13–15]. Such similarity in the formation process of exosomes and lentivirus (LV) prompted some scientists to propose the Trojan exosome hypothesis, which
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