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The recently developed mRNA-based coronavirus SARS-CoV-2 vaccines highlighted the great therapeutic potential of the mRNA technology. Although the lipid nanoparticles used for the delivery of the mRNA are very efficient, they showed, in some cases, the induction of side effects as well as the production of antibodies directed against particle components. Thus, the development of alternative delivery systems is of great interest in the pursuit of more effective mRNA treatments. In the present work, we evaluated the mRNA transfection capacities of a series of cationic histidine-rich amphipathic peptides derived from LAH4. We found that while the LAH4-A1 peptide was an efficient carrier for mRNA, its activity was highly serum sensitive. Interestingly, modification of this cell penetrating peptide at the N-terminus with two tyrosines or with salicylic acid allowed to confer serum resistance to the carrier., (© 2024 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.)

The protein transduction and antimicrobial activities of histidine-rich designer peptides were investigated as a function of their sequence and compared to gene transfection, lentivirus transduction and calcein release activities. In membrane environments, the peptides adopt helical conformations where the positioning of the histidine side chains defines a hydrophilic angle when viewed as helical wheel. The transfection of DNA correlates with calcein release in biophysical experiments, being best for small hydrophilic angles supporting a model where lysis of the endosomal membrane is the limiting factor. In contrast, antimicrobial activities show an inverse correlation suggesting that other interactions and mechanisms dominate within the bacterial system. Furthermore, other derivatives control the lentiviral transduction enhancement or the transport of proteins into the cells. Here, we tested the transport into human cell lines of luciferase (63 kDa) and the ribosome-inactivating toxin saporin (30 kDa). Notably, depending on the protein, different peptide sequences are required for the best results, suggesting that the interactions are manifold and complex. As such, designed LAH4 peptides assure a large panel of biological and biophysical activities whereby the optimal result can be tuned by the physico-chemical properties of the sequences.

Magainin 2 and PGLa are antimicrobial peptides found together in frog skin secretions. When added as a mixture they show an order of magnitude increase in antibacterial activity and in model membrane permeation assays. Here we demonstrate that both peptides can form fibers with beta-sheet/turn signature in ATR-FTIR- and CD-spectroscopic analyses, but with different morphologies in EM images. Whereas, fiber formation results in acute reduction of the antimicrobial activity of the individual peptides, the synergistic enhancement of activity remains for the equimolar mixture of PGLa and magainin 2 also after fibril formation. The biological significance and potential applications of such supramolecular aggregates are discussed., (Copyright © 2020 Juhl, Glattard, Lointier, Bampilis and Bechinger.)

The LAH4 family of amphipathic peptides exhibits pronounced antimicrobial, cell penetrating and nucleic acid transfection activities. Furthermore, variants were designed with potent lentiviral transduction enhancement. When viewed along a helical wheel the four histidines are arranged to form an amphipathic structure. In order to optimize some of these biological activities the number of leucine and alanine residues exposed to the hydrophilic surface was systematically varied which resulted in the design of vectofusin a peptide with strong lentiviral transduction enhancement activities. Here the series of peptides with varying numbers of alanine or leucine residues, respectively, framed by the histidines was tested for their calcein release activity. Interestingly, the membrane pore formation and DNA transfection activities show a clear correlation with the hydrophilic angle. In contrast the membrane partitioning and the propensity to adopt helical conformations was hardly affected as long as the hydrophilic angle did not exceed a limiting value of 150°., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Earth observation technology is a rapidly expanding field in which new outlets for sensor data are being found daily. However medical applications are still limited. The main obstacle is the lack of methods to link spatial data to an epidemiological data base within a given disease context. This obstacle was recently overcome in the Sinfra region of Cote d'Ivoire where a number of researchers have been working on human African trypanosomiasis (HAT) for over ten years. A geographical information system was developed to allow testing of various spatial relationships especially between the population density and disease prevalence using various methods of geostatistical analysis. Spot satellite data was then used to draw a map showing population density. The data base was used to validate processing by explaining the presence of errors due mainly to locality. Finally as a first experimental application for this methodology, a map showing the risk of HAT transmission over the entire Sinfra region was drawn based on satellite data.