Key result
Artificial extension of the adenovirus fiber shaft inhibits infectivity in CAR-positive cell lines without modifying knob-CAR interaction.
Why the study?
Does artificial extension of the adenovirus fiber shaft inhibit infectivity in CAR-positive cell lines?
Does artificial extension of the adenovirus fiber shaft inhibit infectivity in CAR-positive cell lines?
Artificial extension of the adenovirus fiber shaft inhibits infectivity in CAR-positive cell lines without modifying knob-CAR interaction, which may inform the design of adenoviral vectors for gene therapy.
Answers are grounded in this paper and cite their sources.
Suggests fiber shaft tuning for vector specificity; leaves open in vivo and clinical translation.
Recent studies demonstrate that virus-cellular receptor interactions are not the sole determinants of adenovirus (Ad) tropism. It has been shown that the fiber shaft length, which ranges from 6 to 23 beta-repeats in human Ads, also influences viral tropism. However, there is no report that investigates whether artificial extension of the shaft alters the infectivity profile of Ad. Therefore, we constructed Ad serotype 5 (Ad5) capsid-based longer-shafted Ad vectors by incorporating Ad2 shaft fragments of different lengths into the Ad5 shaft. We show that "longer-shafted" Ad vectors (up to 32 beta-repeats) could be rescued. We also show that longer-shafted Ad vectors had no impact on knob-CAR (coxsackievirus and Ad receptor) interaction compared to wild-type Ad. Nevertheless, gene transfer efficiencies of longer-shafted Ad vectors were lower in CAR-positive cell lines compared to wild-type Ad. We suggest that artificial extension of the shaft can inhibit infectivity in the context of CAR-positive cell lines without modification of knob-CAR interaction.
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Seki et al. (2002) studied this question. Artificial extension of the adenovirus fiber shaft (longer-shafted Ad vectors) vs. Wild-type Ad5 vector was evaluated on Gene transfer efficiency (luciferase activity). Artificial extension of the adenovirus fiber shaft inhibits infectivity in CAR-positive cell lines without modifying knob-CAR interaction.
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