Rational design and characterisation of a linear cell penetrating peptide for non-viral gene delivery

McErlean, Emma; Ziminska, Monika; McCrudden, Cian M.; McBride, J.W.; Loughran, Stephen P.; Cole, Grace; Mulholland, Eoghan J.; Kett, Vicky L.; Buckley, Niamh E.; Robson, Tracy; Dunne, Nicholas; McCarthy, Helen

doi:10.1016/j.jconrel.2020.11.037

Cited by 42 publications

(33 citation statements)

References 53 publications

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“…Similarly, Gan and Wang (2007) have demonstrated that increasing the chitosan concentrations could lead to an increase in the solution viscosity which could be a major contributor to the decrease of the EE. Furthermore, the high viscosity associated with increased chitosan concentration hinders EE by deterring the biomolecules movement around chitosan molecular chain [ 17 ]. Concerning the low EE levels observed for the lower polymer ratios, it is suggested that the polymer was insufficient to induce the formation of polyplexes, due to the very low amount of available chitosan, limiting the interaction and encapsulation of pDNA.…”

Section: Resultsmentioning

confidence: 99%

“…The positive surface charge is a very important requirement to be considered for any carrier to be used as an efficient gene delivery system. Moreover, the entry in the intracellular compartment will be simplified if the delivery system presents a small size (<200 nm) [ 16 , 17 ]. Thus, the zeta potential and size of the pDNA-loaded polyplexes were evaluated.…”

Section: Resultsmentioning

confidence: 99%

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Effect of Plasmid DNA Size on Chitosan or Polyethyleneimine Polyplexes Formulation

et al. 2021

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Gene therapy could be simply defined as a strategy for the introduction of a functional copy of desired genes in patients, to correct some specific mutation and potentially treat the respective disorder. However, this straightforward definition hides very complex processes related to the design and preparation of the therapeutic genes, as well as the development of suitable gene delivery systems. Within non-viral vectors, polymeric nanocarriers have offered an ideal platform to be applied as gene delivery systems. Concerning this, the main goal of the study was to do a systematic evaluation on the formulation of pDNA delivery systems based on the complexation of different sized plasmids with chitosan (CH) or polyethyleneimine (PEI) polymers to search for the best option regarding encapsulation efficiency, surface charge, size, and delivery ability. The cytotoxicity and the transfection efficiency of these systems were accessed and, for the best p53 encoding pDNA nanosystems, the ability to promote protein expression was also evaluated. Overall, it was showed that CH polyplexes are more efficient on transfection when compared with the PEI polyplexes, resulting in higher P53 protein expression. Cells transfected with CH/p53-pDNA polyplexes presented an increase of around 54.2% on P53 expression, while the transfection with the PEI/p53-pDNA polyplexes resulted in a 32% increase.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Effect of Plasmid DNA Size on Chitosan or Polyethyleneimine Polyplexes Formulation

et al. 2021

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“…In order to develop the ideal CPP for oligonucleotide delivery, Prof. H. McCarthy's group designed a 15mer CHAT peptide forming PBNs (~200 nm) in the presence of pDNA [56]. This peptide was composed of arginine residues for nucleic acid complexation and cellular uptake, tryptophan to enhance hydrophobic cell membrane interactions, histidine to allow endosomal escape, and cysteine for stability to confer controlled intracellular cargo release through the reduction of disulphide bonds in the intracellular environment.…”

Section: Chatmentioning

confidence: 99%

Peptide-Based Nanoparticles for Therapeutic Nucleic Acid Delivery

et al. 2021

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Gene therapy offers the possibility to skip, repair, or silence faulty genes or to stimulate the immune system to fight against disease by delivering therapeutic nucleic acids (NAs) to a patient. Compared to other drugs or protein treatments, NA-based therapies have the advantage of being a more universal approach to designing therapies because of the versatility of NA design. NAs (siRNA, pDNA, or mRNA) have great potential for therapeutic applications for an immense number of indications. However, the delivery of these exogenous NAs is still challenging and requires a specific delivery system. In this context, beside other non-viral vectors, cell-penetrating peptides (CPPs) gain more and more interest as delivery systems by forming a variety of nanocomplexes depending on the formulation conditions and the properties of the used CPPs/NAs. In this review, we attempt to cover the most important biophysical and biological aspects of non-viral peptide-based nanoparticles (PBNs) for therapeutic nucleic acid formulations as a delivery system. The most relevant peptides or peptide families forming PBNs in the presence of NAs described since 2015 will be presented. All these PBNs able to deliver NAs in vitro and in vivo have common features, which are characterized by defined formulation conditions in order to obtain PBNs from 60 nm to 150 nm with a homogeneous dispersity (PdI lower than 0.3) and a positive charge between +10 mV and +40 mV.

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“…Cell-penetrating peptides (CPPs) belong to a class of short peptides that are able to penetrate across cell membranes and have been demonstrated to facilitate the transfection of nonviral gene delivery vectors [ 131 , 132 , 133 ]. Human immunodeficiency virus (HIV) twin arginine translocation (TAT) peptide is the most commonly used CPP for gene delivery.…”

Section: Nonviral Vectorsmentioning

confidence: 99%

Mesenchymal Stem Cells Engineered by Nonviral Vectors: A Powerful Tool in Cancer Gene Therapy

et al. 2021

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Due to their “tumor homing” and “immune privilege” characteristics, the use of mesenchymal stem cells (MSCs) has been proposed as a novel tool against cancer. MSCs are genetically engineered in vitro and then utilized to deliver tumoricidal agents, including prodrugs and bioactive molecules, to tumors. The genetic modification of MSCs can be achieved by various vectors, and in most cases viral vectors are used; however, viruses may be associated with carcinogenesis and immunogenicity, restricting their clinical translational potential. As such, nonviral vectors have emerged as a potential solution to address these limitations and have gradually attracted increasing attention. In this review, we briefly revisit the current knowledge about MSC-based cancer gene therapy. Then, we summarize the advantages and challenges of nonviral vectors for MSC transfection. Finally, we discuss recent advances in the development of new nonviral vectors, which have provided promising strategies to overcome obstacles in the gene modulation of MSCs.

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Rational design and characterisation of a linear cell penetrating peptide for non-viral gene delivery

Cited by 42 publications

References 53 publications

Effect of Plasmid DNA Size on Chitosan or Polyethyleneimine Polyplexes Formulation

Effect of Plasmid DNA Size on Chitosan or Polyethyleneimine Polyplexes Formulation

Peptide-Based Nanoparticles for Therapeutic Nucleic Acid Delivery

Mesenchymal Stem Cells Engineered by Nonviral Vectors: A Powerful Tool in Cancer Gene Therapy

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