Article
Materials Science, Biomaterials
James E. Noble, Paula Vila-Gomez, Stephanie Rey, Camilla Dondi, Andrea Briones, Purnank Aggarwal, Alex Hoose, Maryana Baran, Maxim G. Ryadnov
Summary: This study cross-compares commercial and experimental transfection reagents from the same family of helical amphiphiles and reveals that despite differences in sequence composition, length, and origin, peptide reagents of the same structural family exhibit similar characteristics and limitations with common variability trends. The functional DNA delivery is found to be independent of the peptide sequence used but is mediated by the ability of the reagents to co-fold with DNA. Peptide folding is proved to be the common determinant for DNA complexation and delivery by peptidic transfection reagents.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
Article
Biochemical Research Methods
Shalini Gupta, Md Qasim, Abhishek Gupta, Jayanta Kundu, Surajit Sinha
Summary: Efficient cytosolic delivery with low toxicity is crucial for developing antisense oligonucleotides or therapeutic peptides as drug candidates for clinical trials. Structural modifications of internal guanidinium transporters significantly affect transfection, toxicity, and endosomal escape, leading to the selection of promising analogues for validation. Detailed mechanistic studies revealed different endocytosis pathways and their variations in cell lines, demonstrating the importance of understanding cellular mechanisms for efficient drug delivery.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Kapilraj Periyasamy, Maria Maloverjan, Abhijit Biswas, Anu Remm, Martin Pook, Ana Rebane, Margus Pooga
Summary: mRNA-based vaccines and candidate therapeutics have potential in various medical fields. In this study, the efficiency and characteristics of cell-penetrating peptide PepFect14 (PF14) and mRNA nanoparticles in different conditions were evaluated. The results showed that PF14-mRNA formulations entered cells and calcium chloride and polysorbate 80 enhanced their transport and protein production. The nanoparticles primarily entered cells via macropinocytosis and clathrin-mediated endocytosis. Subcutaneous injection of PF14-mRNA nanoparticles resulted in protein expression without harmful immune responses in the skin, indicating their potential for mRNA-based therapeutics for inflammatory skin conditions.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Ulo Langel
Summary: In the past 25-30 years, multiple novel mechanisms and applications of cell-penetrating peptides (CPP) have been demonstrated, leading to novel drug delivery systems. Research in the author's own laboratories has led to the development of multiple CPPs, paving the way for delivering bio-functional materials.
Article
Pharmacology & Pharmacy
Heleri H. Hark, Ly Porosk, Lucas R. de Mello, Piret Arukuusk, Emerson R. da Silva, Kaido Kurrikoff
Summary: Despite efforts over the last three decades, there is still a lack of delivery platforms for nucleic acid-based therapeutics in the clinical stage. Cell-penetrating peptides (CPPs) may offer solutions as potential delivery vectors. By designing a kinked structure in the peptide backbone and optimizing the charge distribution, the CPP NF55 has been shown to have potent in vivo activity, making it a potential candidate for delivering nucleic acid-based therapeutics for lung-associated diseases.
Review
Cell Biology
Olga Klaudia Szewczyk-Roszczenko, Piotr Roszczenko, Anna Shmakova, Nataliya Finiuk, Serhii Holota, Roman Lesyk, Anna Bielawska, Yegor Vassetzky, Krzysztof Bielawski
Summary: Endocytosis is a major cellular communication process that can be hijacked by pathogens and involved in oncogenic transformation. This review explores different approaches to inhibit endocytosis, discusses chemical inhibitors, and explores potential clinical applications.
Article
Pharmacology & Pharmacy
Daniel P. Morris, Lucy C. Snipes, Stephanie A. Hill, Michael M. Woods, Maria M. Mbugua, Lydia R. Wade, Jonathan L. McMurry
Summary: Cell penetrating peptides (CPPs) are a promising technology for delivering therapeutic macromolecule cargos. This study investigates the role of cargo charge in CPP effectiveness and introduces a new method for combinatorial assays of adaptors and cargos to identify enhanced internalization efficiency and other properties.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Maria Maloverjan, Kaert Padari, Aare Abroi, Ana Rebane, Margus Pooga
Summary: This study reveals that the incorporation of calcium and magnesium ions into CPP-oligonucleotide nanoparticles can enhance transfection efficiency without increasing cytotoxicity. This discovery may contribute to improving the efficacy of CPP-mediated transfection in clinical applications.
Article
Pharmacology & Pharmacy
Ly Porosk, Jekaterina Nebogatova, Heleri Heike Hark, Birgit Vunk, Piret Arukuusk, Urve Toots, Mart Ustav, Ulo Langel, Kaido Kurrikoff
Summary: Therapeutic proteins are at the forefront of innovation in pharmaceutical medicine, but their industrial production poses technical challenges. This study aimed to find a fast, microliter-scale transfection assay for predicting protein expression in transient production settings. The results showed that commonly used microliter-scale transfection efficacy assays fail to predict performance in large-scale protein production. Additionally, cell-penetrating peptide-based transfection achieved significantly higher protein yields compared to other methods.
Article
Biochemical Research Methods
Fang Tang, Qian Wang, Yi-Nan Gao, Yu-Shan Zhang, Ya-Xuan Liang, Zhong-Lin Lu, Rui Liu, Ai-Xiang Ding
Summary: In this study, a nonviral gene vector with low cytotoxicity, visual tracking ability, and high serum tolerance was constructed using the combination of fluorination and aggregation-induced emission (AIE). The vector, FluoTPA, showed effective delivery of nucleic acids into cells and achieved comparable transfection efficiency under high serum content. The results suggest that FluoTPA could be a reliable theranostic platform for nonviral nucleic acid therapeutics in serum condition.
BIOCONJUGATE CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Ly Porosk, Ulo Langel
Summary: Cell penetrating peptides (CPPs) are short peptides that can cross cell membranes and facilitate the delivery of drugs and other cargo. Various research tools from chemistry, physics, molecular biology, and engineering have been used to evaluate and characterize CPP-based delivery systems.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Saeed Anwar, Farin Mir, Toshifumi Yokota
Summary: Oligonucleotide-based therapies have potential in treating hard-to-treat diseases, especially genetic and rare diseases. Overcoming the challenge of ensuring uptake by target cells/tissues involves strategies such as cell-penetrating peptide conjugation, chemical modification, nanoparticle formulation, and the use of endogenous vesicles, spherical nucleic acids, and smart material-based delivery vehicles. This article provides an overview of these strategies, their potential, safety considerations, regulatory requirements, and challenges in translating these therapies from the laboratory to the clinic.
Review
Biochemistry & Molecular Biology
Sachon Emmanuelle, Walrant Astrid, Sagan Sandrine, Cribier Sophie, Rodriguez Nicolas
Summary: Antimicrobial and cell-penetrating peptides have been extensively studied for over 60 years, initially separately and more recently in parallel. These studies have led to methodological advancements in observation techniques and membrane models, including the development of droplet interface bilayers, new fluorescence approaches, force measurements, and photolabelling techniques.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Safa Bazaz, Tonis Lehto, Rahel Tops, Olof Gissberg, Dhanu Gupta, Burcu Bestas, Jeremy Bost, Oscar P. B. Wiklander, Helena Sork, Eman M. Zaghloul, Doste R. Mamand, Mattias Hallbrink, Rannar Sillard, Osama Saher, Kariem Ezzat, C. I. Edvard Smith, Samir El Andaloussi, Taavi Lehto
Summary: Splice-switching therapy with SSOs has shown promise for treating mis-splice disorders, but limited by poor bioavailability. Cell-penetrating peptides have gained attention for improving delivery of oligonucleotide compounds. By introducing hydrophobic modifications using hydrocarbon-modified amino acids, CPPs can effectively formulate SSOs into NPs for improved delivery efficacy in vitro and in vivo.
Article
Biochemistry & Molecular Biology
Betty Revon Liu, Shiow-Her Chiou, Yue-Wern Huang, Han-Jung Lee
Summary: Recently, membrane-active peptides or proteins, especially cell-penetrating peptides (CPPs), have attracted attention due to their potential applications in drug delivery. In this review, we focused on arginine-rich CPPs and discussed their mechanisms for intracellular uptake. The amino acid sequence is a key factor that determines the cellular internalization mechanism. CPPs are non-cytotoxic and widely applicable, making them a trending tool for cellular delivery.