Histidylated Lipid-modified Sendai Viral Envelopes Mediate Enhanced Membrane Fusion and Potentiate Targeted Gene Delivery

Verma, Santosh Kumar; Mani, Prashant; Sharma, Nisha; Krishnan, Anuja; Kumar, Valluripalli Vinod; Reddy, B. S. Praveen; Chaudhuri, Arabinda; Roy, Rajendra P.; Sarkar, Debi P.

doi:10.1074/jbc.m506615200

Cited by 21 publications

(28 citation statements)

References 32 publications

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“…The role of a "histidylated" lipid in promoting membrane fusion of reconstituted SeV envelope (FV) with liver cells in culture and in whole animal has been established (45). This kind of fusion enhancement is analogous to HN-mediated fusion promotion of F glycoprotein for paramyxovirus family, and so we decided to identify specific "histidine" residue(s) of the HN glycoprotein that might be involved in fusion promotion.…”

Section: Construction and Expression Of Histidine Mutants Of Hn Protementioning

confidence: 99%

“…The fusion efficiency of FV increased on cografting a histidyl residue of a cationic amphiphile (L H ) in the virosome membrane (L H F-virosome) (45). It has been proposed that L H probably activates F protein into a more fusion competent state by stabilizing the coiled-coil heptad repeats of F protein, leading to enhanced membrane fusion.…”

mentioning

confidence: 99%

“…To see the effect of SH and SA peptides on the FV-HepG2 cell fusion, NBD-PE-FV was coincubated with HepG2 cells in the presence of 10 M SH or SA on ice for 60 min to allow binding, and then the fusion kinetics with HepG2 cells were evaluated as described above. The effect of peptides (SH/SA and PH/PA) on fusion activity was also tested by hemolysis assay and delivery of RITClysozyme into HepG2 (content-mixing assay) cells through NBD-PE-FV according to our published protocols (3,45).…”

mentioning

confidence: 99%

“…SeV FV (20 g), preincubated with 10 M SH or SA peptides, was treated with proteinase K (0.05 g/ml) at 37°C for 30 min, and the extent of digestion was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE; reducing gel). It was further analyzed by densitometric scanning using ImageMaster total lab software (version 1.11; Amersham Pharmacia Biotech) (45). This was cross-checked by Western blot analysis using F-specific antibody.…”

mentioning

confidence: 99%

“…NBD-PE-labeled FV (NBD-PE-FV) were prepared, and its fusion in the presence of peptides with human liver cells in culture was carried out as described earlier (3,45). Spectrofluorimetric measurements of membrane fusion were performed as described above.…”

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confidence: 99%

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A Histidine Switch in Hemagglutinin-Neuraminidase Triggers Paramyxovirus-Cell Membrane Fusion

Krishnan

Verma

Mani

et al. 2009

J Virol

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Most paramyxovirus fusion proteins require coexpression of and activation by a homotypic attachment protein, hemagglutinin-neuraminidase (HN), to promote membrane fusion. However, the molecular mechanism of the activation remains unknown. We previously showed that the incorporation of a monohistidylated lipid into F-virosome (Sendai viral envelope containing only fusion protein) enhanced its fusion to hepatocytes, suggesting that the histidine residue in the lipid accelerated membrane fusion. Therefore, we explored whether a histidine moiety in HN could similarly direct activation of the fusion protein. In membrane fusion assays, the histidine substitution mutants of HN (H247A of Sendai virus and H245A of human parainfluenza virus 3) had impaired membrane fusion promotion activity without significant changes in other biological activities. Synthetic 30-mer peptides corresponding to regions of the two HN proteins containing these histidine residues rescued the fusion promoting activity of the mutants, whereas peptides with histidine residues substituted by alanine did not. These histidine-containing peptides also activated F-virosome fusion with hepatocytes both in the presence and in the absence of mutant HN in the virosome. We provide evidence that the HN-mimicking peptides promote membrane fusion, revealing a specific histidine "switch" in HN that triggers fusion.

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Section: Construction and Expression Of Histidine Mutants Of Hn Protementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A Histidine Switch in Hemagglutinin-Neuraminidase Triggers Paramyxovirus-Cell Membrane Fusion

Krishnan

Verma

Mani

et al. 2009

J Virol

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Noncationic Material Design for Nucleic Acid Delivery

Jiang

Thayumanavan

2020

Advanced Therapeutics

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Nucleic acid delivery provides effective options to control intracellular gene expression and protein production. Efficient delivery of nucleic acid typically requires delivery vehicles to facilitate the entry of nucleic acid into cells. Among nonviral delivery vehicles, cationic materials are favored because of their high loading capacity for nucleic acids and prominent cellular uptake efficiency through electrostatic interactions. However, cationic moieties at high dosage tend to induce severe cytotoxicity due to interference with cell membrane integrity. In contrast, noncationic materials present alternative delivery approaches with less safety concerns than cationic materials. In this Progress Report, principles of noncationic material design for nucleic acid delivery are discussed. Examples of such noncationic platforms are highlighted, including complexation or conjugation with nucleic acids and self‐assembled nucleic acid structures.

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Long-term reduction of jaundice in Gunn rats by nonviral liver-targeted delivery of Sleeping Beauty transposon

et al. 2009

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Asialoglycoprotein receptor (ASGPR)-mediated endocytosis has been used to target genes to hepatocytes in vivo. However, the level and duration of transgene expression have been low because of lysosomal translocation and degradation of the DNA and lack of its integration into the host genome. In this study we packaged the DNA of interest in proteoliposomes containing the fusogenic galactose-terminated F-glycoprotein of the Sendai virus (FPL) for targeted delivery to hepatocytes. After the FPL binds to ASGPR on the hepatocyte surface, fusogenic activity of the F-protein delivers the DNA into the cytosol, bypassing the endosomal pathway. For transgene integration we designed plasmids containing one transcription unit expressing the Sleeping Beauty transposase (SB) and another expressing human uridinediphosphoglucuronate glucuronosyltransferase-1A1 (pSB-hUGT1A1). The latter was flanked by inverted/direct repeats that are substrates of SB. In cell culture, FPL-mediated delivery of the E. coli β-galactosidase gene (LacZ) resulted in transduction of ASGPR-positive cells (rat hepatocytes or Hepa1 cell line), but not of ASGPR-negative 293 cells. Intravenous injection of the FPL-entrapped pSB-hUGT1A1 (4–8 μg/day, 1–4 doses) into UGT1A1-deficient hyperbilirubinemic Gunn rats (model of Crigler-Najjar syndrome type 1) resulted in hUGT1A1 expression in 5%–10% of hepatocytes, but not in other cell types. Serum bilirubin levels declined by 30% ± 4% in 2 weeks and remained at that level throughout the 7-month study duration. With histidine containing FPL, serum bilirubin was reduced by 40% ± 5%, and bilirubin glucuronides were excreted into bile. No antibodies were detectable in the recipient rats against the F-protein or human UGT1A1. Conclusion FPL is an efficient hepatocyte-targeted gene delivery platform in vivo that warrants further exploration toward clinical application.

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Histidylated Lipid-modified Sendai Viral Envelopes Mediate Enhanced Membrane Fusion and Potentiate Targeted Gene Delivery

Cited by 21 publications

References 32 publications

A Histidine Switch in Hemagglutinin-Neuraminidase Triggers Paramyxovirus-Cell Membrane Fusion

A Histidine Switch in Hemagglutinin-Neuraminidase Triggers Paramyxovirus-Cell Membrane Fusion

Noncationic Material Design for Nucleic Acid Delivery

Long-term reduction of jaundice in Gunn rats by nonviral liver-targeted delivery of Sleeping Beauty transposon

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