Gene therapy with RALA/iNOS composite nanoparticles significantly enhances survival in a model of metastatic prostate cancer

McCrudden, Cian M.; McBride, J.W.; McCaffrey, Joanne; McErlean, Emma; Dunne, Nicholas; Kett, Vicky L.; Coulter, Jonathan A.; Robson, Tracy; McCarthy, Helen

doi:10.1186/s12645-018-0040-x

Cited by 29 publications

(14 citation statements)

References 29 publications

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“…Modification of the RALA sequence in terms of amino acid composition and sequence length failed to improve the functional characteristics of RALA, confirming its superior sequence for non-toxic gene delivery [82]. RALA is a widely used peptidebased delivery system, mainly optimized for the transfection of different oligonucleotides such as plasmids [34,83,84], siRNA [35][36][37], mRNA [38], and for DNA vaccination [85], demonstrating its broad utility.…”

Section: Gala/kala/rala Familymentioning

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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Section: Gala/kala/rala Familymentioning

confidence: 99%

Peptide-Based Nanoparticles for Therapeutic Nucleic Acid Delivery

et al. 2021

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“…As a consequence, pore formation, membrane fusion, and/or lysis are induced. Their membrane lytic activity explains extensive utilization of these fusogenic peptide in modulating non-viral gene delivery systems [76,[162][163][164][165][166]. Similar to GALA, JTS-1, a negatively charged amphipathic peptide with strong nonpolar amino acids in the hydrophobic domain and glutamic acid residues in the hydrophilic domain is able to form an α-helical structure [167].…”

Section: Fusogenic Peptidesmentioning

confidence: 99%

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

Tarvirdipour

Skowicki

Schoenenberger

et al. 2021

IJMS

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Concerns associated with nanocarriers’ therapeutic efficacy and side effects have led to the development of strategies to advance them into targeted and responsive delivery systems. Owing to their bioactivity and biocompatibility, peptides play a key role in these strategies and, thus, have been extensively studied in nanomedicine. Peptide-based nanocarriers, in particular, have burgeoned with advances in purely peptidic structures and in combinations of peptides, both native and modified, with polymers, lipids, and inorganic nanoparticles. In this review, we summarize advances on peptides promoting gene delivery systems. The efficacy of nucleic acid therapies largely depends on cell internalization and the delivery to subcellular organelles. Hence, the review focuses on nanocarriers where peptides are pivotal in ferrying nucleic acids to their site of action, with a special emphasis on peptides that assist anionic, water-soluble nucleic acids in crossing the membrane barriers they encounter on their way to efficient function. In a second part, we address how peptides advance nanoassembly delivery tools, such that they navigate delivery barriers and release their nucleic acid cargo at specific sites in a controlled fashion.

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“…Arginine-rich peptides are similarly conducive to tight gene condensation, and due to their ability to promote cell penetration, they are effective delivery systems [109,110]. RALA, an amphipathic, cell penetrating peptide with seven arginines in its backbone, formed peptiplexes with siRNA as well as pDNA, which were used as delivery platform in vitro and in vivo ( Figure 7) [111][112][113][114]. By the same token, hydrophilic histidine residues due to their positive charge at physiological pH, bind and condense nucleic acids in aqueous solution [115].…”

Section: Nanoparticlesmentioning

confidence: 99%

Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application

et al. 2020

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Nanotechnology approaches play an important role in developing novel and efficient carriers for biomedical applications. Peptides are particularly appealing to generate such nanocarriers because they can be rationally designed to serve as building blocks for self-assembling nanoscale structures with great potential as therapeutic or diagnostic delivery vehicles. In this review, we describe peptide-based nanoassemblies and highlight features that make them particularly attractive for the delivery of nucleic acids to host cells or improve the specificity and sensitivity of probes in diagnostic imaging. We outline the current state in the design of peptides and peptide-conjugates and the paradigms of their self-assembly into well-defined nanostructures, as well as the co-assembly of nucleic acids to form less structured nanoparticles. Various recent examples of engineered peptides and peptide-conjugates promoting self-assembly and providing the structures with wanted functionalities are presented. The advantages of peptides are not only their biocompatibility and biodegradability, but the possibility of sheer limitless combinations and modifications of amino acid residues to induce the assembly of modular, multiplexed delivery systems. Moreover, functions that nature encoded in peptides, such as their ability to target molecular recognition sites, can be emulated repeatedly in nanoassemblies. Finally, we present recent examples where self-assembled peptide-based assemblies with “smart” activity are used in vivo. Gene delivery and diagnostic imaging in mouse tumor models exemplify the great potential of peptide nanoassemblies for future clinical applications.

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Gene therapy with RALA/iNOS composite nanoparticles significantly enhances survival in a model of metastatic prostate cancer

Cited by 29 publications

References 29 publications

Peptide-Based Nanoparticles for Therapeutic Nucleic Acid Delivery

Peptide-Based Nanoparticles for Therapeutic Nucleic Acid Delivery

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application

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