tetano
Editor, Senior Moderator
Bioconjug Chem. 2017 Jun 21. doi: 10.1021/acs.bioconjchem.7b00124. [Epub ahead of print]
[h=1]A delivery system targeting haemagglutinin of influenza virus A to facilitate antisense-based anti-H1N1 therapy.[/h] Ding X, Yang J, Lu D, Li Q, Zhang Z, Zhou Z, Wang S.
[h=3]Abstract[/h] Antisense oligonucleotides (ODNs) are therapeutic molecules that hybridize to complementary target mRNA sequences. To further overcome the poor cellular uptake of ODNs, we proposed a novel strategy to deliver ODNs by conjugating the anti-influenza A virus (IAV) ODN with a peptide showing high affinity to the haemagglutinin (HA) on the surface of IAV particles or the IAV infected host cells. The HA-specific binding peptides were selected by phage display and the individual binding clones are characterized by DNA sequencing, and the selected phage was further assayed by ELISA. The final selected HA-binding peptide, SHGRITFAYFAN, was conjugated to an anti-IAV ODN. The delivery efficiency and the anti-IAV effects of the conjugated molecule were evaluated in a cell culture and a mouse infection model. The conjugated molecule was successfully delivered into IAV-infected host cells more efficiently than the anti-IAV ODN in vitro and in vivo. Furthermore, the conjugated molecule protected 80% of the mice from lethal challenge and inhibited the plaque count by 75%, compared to the un-conjugated molecule (60% and 40%). These findings demonstrate that the delivery of antisense oligodeoxynucleotides to infected tissues by a virus-binding peptide-mediated system is a potential therapeutic strategy against IAV.
PMID: 28635259 DOI: 10.1021/acs.bioconjchem.7b00124
[h=1]A delivery system targeting haemagglutinin of influenza virus A to facilitate antisense-based anti-H1N1 therapy.[/h] Ding X, Yang J, Lu D, Li Q, Zhang Z, Zhou Z, Wang S.
[h=3]Abstract[/h] Antisense oligonucleotides (ODNs) are therapeutic molecules that hybridize to complementary target mRNA sequences. To further overcome the poor cellular uptake of ODNs, we proposed a novel strategy to deliver ODNs by conjugating the anti-influenza A virus (IAV) ODN with a peptide showing high affinity to the haemagglutinin (HA) on the surface of IAV particles or the IAV infected host cells. The HA-specific binding peptides were selected by phage display and the individual binding clones are characterized by DNA sequencing, and the selected phage was further assayed by ELISA. The final selected HA-binding peptide, SHGRITFAYFAN, was conjugated to an anti-IAV ODN. The delivery efficiency and the anti-IAV effects of the conjugated molecule were evaluated in a cell culture and a mouse infection model. The conjugated molecule was successfully delivered into IAV-infected host cells more efficiently than the anti-IAV ODN in vitro and in vivo. Furthermore, the conjugated molecule protected 80% of the mice from lethal challenge and inhibited the plaque count by 75%, compared to the un-conjugated molecule (60% and 40%). These findings demonstrate that the delivery of antisense oligodeoxynucleotides to infected tissues by a virus-binding peptide-mediated system is a potential therapeutic strategy against IAV.
PMID: 28635259 DOI: 10.1021/acs.bioconjchem.7b00124