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- W2793200609 abstract "Peptides and peptide nucleic acids (PNAs) have long been recognized as promising tools and potential therapeutics. Yet the cell membrane remains a significant barrier to their intracellular targets. Conjugation to cell penetrating peptides (CPPs) like pTat48-60 (tat) and pAntp43-68 (penetratin) facilitates delivery, however delivery efficiencies remain low. Improving the performance of known CPPs by rational design is hindered by the lack of explicit design principles. Instead, here we use synthetic molecular evolution (SME) to generate and screen a CPP library containing 8,192 tat/penetratin hybrid peptides to identify sequences with improved ability to deliver PNA, using the Hela pTRE-LucIVS2 (Hela705) system. The parent sequences poorly deliver PNA705 to cells. However, at 5μM peptide-PNA, the top performing Delivery Peptide (PDEP)-PNA705 daughter sequence showed an 80-fold increase over PNA705 only treated cells in properly spliced luciferase mRNA (qRT-PCR) and 33-fold higher standardized luminescence values than the top performing parent sequence penetratin. The PDEPs identified in this study are effective in multiple cell types, and deliver a peptide cargo to cells. The capabilities of the PDEPs make them a valuable research tool for delivery of membrane impermeable PNA or peptide sequences. This dramatic improvement in performance following a single iteration of SME is an indication of the power of this approach to peptide sequence optimization." @default.
- W2793200609 created "2018-03-29" @default.
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- W2793200609 date "2018-02-01" @default.
- W2793200609 modified "2023-09-27" @default.
- W2793200609 title "Synthetic Molecular Evolution of Hybrid Cell Penetrating Peptides that Efficiently Deliver Peptide and Peptide Nucleic Acid Cargoes to Cells" @default.
- W2793200609 doi "https://doi.org/10.1016/j.bpj.2017.11.1542" @default.
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