Design and Evaluation of Histidine-Rich Amphipathic Peptides for siRNA Delivery

Langlet-Bertin, Bérangère; Leborgne, Christian; Scherman, Daniel; Bechinger, Burkhard; Mason, A. James; Kichler, Antoine

doi:10.1007/s11095-010-0138-2

Cited by 89 publications

(120 citation statements)

References 32 publications

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“…These data underline the fact that these two functions likely rely on different critical molecular determinants. Cell Line Transfection with Vectofusin-1 Derivatives-LAH4 derivatives have been described previously as nucleic acid transfection agents (31)(32)(33)43). Therefore, we tested the capacity of Vectofusin-1 and some derivatives to transfect 293T cells with an eGFP-expressing plasmid.…”

Section: Evaluation Of Vectofusin-1 Activity On Lentiviral Transductimentioning

confidence: 99%

Molecular Determinants of Vectofusin-1 and Its Derivatives for the Enhancement of Lentivirally Mediated Gene Transfer into Hematopoietic Stem/Progenitor Cells

Majdoul

Seye

Kichler

et al. 2016

Journal of Biological Chemistry

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Gene delivery into hCD34؉ hematopoietic stem/progenitor cells (HSPCs) using human immunodeficiency virus, type 1-derived lentiviral vectors (LVs) has several promising therapeutic applications. Numerous clinical trials are currently underway. However, the efficiency, safety, and cost of LV gene therapy could be ameliorated by enhancing target cell transduction levels and reducing the amount of LV used on the cells. Several transduction enhancers already exist, such as fibronectin fragments or cationic compounds. Recently, we discovered Vectofusin-1, a new transduction enhancer, also called LAH4-A4, a short histidine-rich amphipathic peptide derived from the LAH4 family of DNA transfection agents. Vectofusin-1 enhances the infectivity of lentiviral and ␥-retroviral vectors pseudotyped with various envelope glycoproteins. In this study, we compared a family of Vectofusin-1 isomers and showed that Vectofusin-1 remains the lead peptide for HSPC transduction enhancement with LVs pseudotyped with vesicular stomatitis virus glycoproteins and also with modified gibbon ape leukemia virus glycoproteins. By comparing the capacity of numerous Vectofusin-1 variants to promote the modified gibbon ape leukemia virus glycoprotein-pseudotyped lentiviral vector infectivity of HSPCs, the lysine residues on the N-terminal extremity of Vectofusin-1, a hydrophilic angle of 140°formed by the histidine residues in the Schiffer-Edmundson helical wheel representation, hydrophobic residues consisting of leucine were all found to be essential and helped to define a minimal active sequence. The data also show that the critical determinants necessary for lentiviral transduction enhancement are partially different from those necessary for efficient antibiotic or DNA transfection activity of LAH4 derivatives. In conclusion, these results help to decipher the action mechanism of Vectofusin-1 in the context of hCD34؉ cell-based gene therapy.

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Section: Evaluation Of Vectofusin-1 Activity On Lentiviral Transductimentioning

confidence: 99%

Molecular Determinants of Vectofusin-1 and Its Derivatives for the Enhancement of Lentivirally Mediated Gene Transfer into Hematopoietic Stem/Progenitor Cells

Majdoul

Seye

Kichler

et al. 2016

Journal of Biological Chemistry

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“…In an acidic environment, peptides are released from the complexes and change their conformation enabling membrane destabilising activity. Subsequently, nucleic acids are released from the endosomal/ lysosomal compartments into the cytoplasm [15,17]. Our previous study has demonstrated that the pH responsive peptides are capable of mediating both highly efficient DNA or siRNA transfection in mammalian cell lines [15] (Abbate et al, unpublished).…”

Section: Introductionmentioning

confidence: 99%

Formulation of pH responsive peptides as inhalable dry powders for pulmonary delivery of nucleic acids

Liang

Kwok

Chow

et al. 2014

European Journal of Pharmaceutics and Biopharmaceutics

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Nucleic acids have the potential to be used as therapies or vaccines for many different types of disease but delivery remains the most significant challenge to their clinical adoption. pH responsive peptides containing either histidine or derivatives of 2,3-diaminopropionic acid (Dap) can mediate effective DNA transfection in lung epithelial cells with the latter remaining effective even in the presence of lung surfactant containing bronchoalveolar fluid (BALF), making this class of peptides attractive candidates for delivering nucleic acids to lung tissues. To further assess the suitability of pH responsive peptides for pulmonary delivery by inhalation, dry powder formulations of pH responsive peptides and plasmid DNA, with mannitol as carrier, were produced by either spray drying (SD) or spray freeze drying (SFD). The properties of the two types of powders were characterised and compared using scanning electron microscopy (SEM), next generation impaction (NGI), gel retardation and in vitro transfection via a twin-stage impinger (TSI) following aerosolisation by a dry powder inhaler (Osmohaler™). Although the aerodynamic performance and transfection efficacy of both powders were good, the overall performance revealed SD powders to have a number of advantages over SFD powders and are the more effective formulation with potential for efficient nucleic acid delivery through inhalation.

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“…Interestingly, more recent investigations show that derivatives of LAH4 exhibit potent antimicrobial action against a number of pathogens found in clinical environments, and these activities are quite pronounced when the peptides occur in orientations parallel to the membrane surface . Furthermore the LAH4 sequences are also capable to transport big hydrophilic cargo such as DNA and RNA across the hydrophobic interior of membranes and thereby exhibit potent transfection capacities (Kichler et al, 2003;Langlet-Bertin et al, 2010;. Because of these important biological activities the thermodynamics of the peptides' interactions with membranes and nucleic acids were investigated in considerable detail and these investigations shall be presented in the following.…”

Section: The Lah4 Family Of Peptidesmentioning

confidence: 99%

“…Furthermore, it was recently shown that they are potent siRNA delivery vehicles with efficiencies that are higher than those of several well-established compounds such as Lipofectamine, DOTAP and polyethylenimine (Langlet-Bertin et al, 2010). In our laboratory a number of biophysical investigations have been performed, supported by many biochemical studies by our longstanding collaborators, which aimed at understanding the mechanisms of these transfection activities.…”

Section: Interactions Of Lah4 Peptides With Dnamentioning

confidence: 99%

Equilibria Governing the Membrane Insertion of Polypeptides and Their Interactions with Other Biomacromolecules

Aisenbrey¹,

Bechinger²

2011

Thermodynamics - Kinetics of Dynamic Systems

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Design and Evaluation of Histidine-Rich Amphipathic Peptides for siRNA Delivery

Abstract: The LAH4 histidine-rich cationic amphipathic peptides represent an interesting and promising family of compounds for siRNA delivery.

Cited by 89 publications

References 32 publications

Molecular Determinants of Vectofusin-1 and Its Derivatives for the Enhancement of Lentivirally Mediated Gene Transfer into Hematopoietic Stem/Progenitor Cells

Molecular Determinants of Vectofusin-1 and Its Derivatives for the Enhancement of Lentivirally Mediated Gene Transfer into Hematopoietic Stem/Progenitor Cells

Formulation of pH responsive peptides as inhalable dry powders for pulmonary delivery of nucleic acids

Equilibria Governing the Membrane Insertion of Polypeptides and Their Interactions with Other Biomacromolecules

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