Cell-penetrating peptides in the intracellular delivery of viral nanoparticles

Hejtmánková, Alžběta; Váňová, Jana; Španielová, Hana

doi:10.1016/bs.vh.2021.06.010

Cited by 5 publications

(3 citation statements)

References 118 publications

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“…CPPs are short peptides that have properties to act as a carrier to deliver biomolecules into diverse prokaryotic and eukaryotic cells. In bacteria, CPPs have been employed for the delivery of numerous biomolecules, including nucleic acid, small compounds and proteins [31][32][33]. PNAs, on the other hand, are nucleotide analogues with an artificial peptide backbone comprising N-2-aminoethylglycine repeats that show strong binding affinity to DNA and RNA and resistance to intracellular enzymes including nucleases and proteases [34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Cell-Penetrating Peptide–Peptide Nucleic Acid Conjugates as a Tool for Protein Functional Elucidation in the Native Bacterium

et al. 2022

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Approximately 30% or more of the total proteins annotated from sequenced bacteria genomes are annotated as hypothetical or uncharacterized proteins. However, elucidation on the function of these proteins is hindered by the lack of simple and rapid screening methods, particularly with novel or hard-to-transform bacteria. In this report, we employed cell-penetrating peptide (CPP) –peptide nucleotide acid (PNA) conjugates to elucidate the function of such uncharacterized proteins in vivo within the native bacterium. Paenibacillus, a hard-to-transform bacterial genus, was used as a model. Two hypothetical genes showing amino acid sequence similarity to ι-carrageenases, termed cgiA and cgiB, were identified from the draft genome of Paenibacillus sp. strain YYML68, and CPP–PNA probes targeting the mRNA of the acyl carrier protein gene, acpP, and the two ι-carrageenase candidate genes were synthesized. Upon direct incubation of CPP–PNA targeting the mRNA of the acpP gene, we successfully observed growth inhibition of strain YYML68 in a concentration-dependent manner. Similarly, both the function of the candidate ι-carrageenases were also inhibited using our CPP–PNA probes allowing for the confirmation and characterization of these hypothetical proteins. In summary, we believe that CPP–PNA conjugates can serve as a simple and efficient alternative approach to characterize proteins in the native bacterium.

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Section: Discussionmentioning

confidence: 99%

Cell-Penetrating Peptide–Peptide Nucleic Acid Conjugates as a Tool for Protein Functional Elucidation in the Native Bacterium

et al. 2022

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“…Fueled by promising proof-of-concept results, CPP sequences have been extensively explored for cytosolic delivery of therapeutic biomolecules including small molecules and nucleic acids as well as larger cargo such as nanoparticles. The first CPPs discovered were linear peptides derived from viruses [ 93 ]. Notably, the Trans-Activator of Transcription (TAT) protein is an 81-amino-acid protein critical to the lifecycle of Human Immunodeficiency Virus (HIV).…”

Section: Methods For Intracellular Protein Deliverymentioning

confidence: 99%

Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications

Chan,

Tsourkas

2024

BME Front

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Protein biologics are powerful therapeutic agents with diverse inhibitory and enzymatic functions. However, their clinical use has been limited to extracellular applications due to their inability to cross plasma membranes. Overcoming this physiological barrier would unlock the potential of protein drugs for the treatment of many intractable diseases. In this review, we highlight progress made toward achieving cytosolic delivery of recombinant proteins. We start by first considering intracellular protein delivery as a drug modality compared to existing Food and Drug Administration-approved drug modalities. Then, we summarize strategies that have been reported to achieve protein internalization. These techniques can be broadly classified into 3 categories: physical methods, direct protein engineering, and nanocarrier-mediated delivery. Finally, we highlight existing challenges for cytosolic protein delivery and offer an outlook for future advances.

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“…These properties are particularly desirable in the case of macromolecules of therapeutic interest, which are otherwise poorly permeable through biological membranes. [1][2][3] Hundreds of studies and reports have shown that CPPs as are excellent tools for promoting intracellular delivery of a wide range of bioactive molecules, including oligonucleotides, siRNA [4,5] anticancer drugs, [6] bioimaging agents, [7][8][9] DNA, nanoparticles, [10][11][12] proteins, [1,13] and other peptides. This broad potential of applications is witnessed by several ongoing studies and clinical trials that confirm its success both in vitro and in vivo applications.…”

Section: Introductionmentioning

confidence: 99%

Cell Penetrating Peptides: Classification, Mechanisms, Methods of Study, and Applications

et al. 2023

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Cell‐penetrating peptides (CPPs) encompass a class of peptides that possess the remarkable ability to cross cell membranes and deliver various types of cargoes, including drugs, nucleic acids, and proteins, into cells. For this reason, CPPs are largely investigated in drug delivery applications in the context of many diseases, such as cancer, diabetes, and genetic disorders. While sharing this functionality and some common structural features, such as a high content of positively charged amino acids, CPPs represent an extremely diverse group of elements, which can differentiate under many aspects. In this review, we summarize the most common characteristics of CPPs, introduce their main distinctive features, mechanistic aspects that drive their function, and outline the most widely used techniques for their structural and functional studies. We highlight current gaps and future perspectives in this field, which have the potential to significantly impact the future field of drug delivery and therapeutics.

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Cell-penetrating peptides in the intracellular delivery of viral nanoparticles

Cited by 5 publications

References 118 publications

Cell-Penetrating Peptide–Peptide Nucleic Acid Conjugates as a Tool for Protein Functional Elucidation in the Native Bacterium

Cell-Penetrating Peptide–Peptide Nucleic Acid Conjugates as a Tool for Protein Functional Elucidation in the Native Bacterium

Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications

Cell Penetrating Peptides: Classification, Mechanisms, Methods of Study, and Applications

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