Peptide Nanoparticles for Gene Packaging and Intracellular Delivery

Vila-Gómez, Paula; Noble, James; Ryadnov, Maxim G.

doi:10.1007/978-1-0716-0928-6_3

Cited by 7 publications

(4 citation statements)

References 26 publications

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“…As an exemplar, the LBF is actively engaged in an Industrial Strategy Challenge Fund (ISCF) project with the National Physical Laboratory (NPL) through the Virtual Metrology and Standards Centre for Engineering Biology that was established in 2018 ( 17 ). A high-throughput cell-free platform for intracellular measurements in miniaturized format is currently being developed alongside NPL biometrology scientists, with whom we are also generating candidate reference materials and biosynthesis protocols ( 18–20 ). Through a series of workshops, we are also exploring a number of key technical, regulatory and societal challenges to enable the development and adoption of standards in synthetic biology, as well as how these could be implemented by our industrial stakeholders ( 14 , 15 ).…”

Section: Standards and Metrology Agendamentioning

confidence: 99%

Biofoundries are a nucleating hub for industrial translation

Farzaneh

Freemont

2021

Synthetic Biology

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Contemporary synthetic biology embraces the entire innovation pipeline; it’s a transformative technology platform impacting new applications and improving existing industrial products and processes. However, challenges still emerge at the interface of up-stream and down-stream processes, integral to the value chain. It is now clear that biofoundries have a key role to play in addressing this; they provide unique and accessible infrastructure to drive the standardization necessary to deliver systematic design and engineering of biological systems and workflows. As for other biofoundries, the success of the London Biofoundry has been in part due to its expertise in establishing channels for industrial translation through its extensive strategic collaborations. It has also become cemented as a key component of various consortia and partnerships that serve the broader bioeconomy and industrial strategies. Adopting a networked approach enables links to be made between infrastructure, researchers, industrialists and policy makers to de-risk the economic challenges of scale-up, as well as contribute to the growing bioeconomy.

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Section: Standards and Metrology Agendamentioning

confidence: 99%

Biofoundries are a nucleating hub for industrial translation

Farzaneh

Freemont

2021

Synthetic Biology

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“…The complexes can be prone to structural polymorphism to a greater extent than viruses but tend to be more straightforward to manufacture and offer virtually unlimited packaging capacity and low safety risks. Among many chemistries used, cationic amphipathic peptides represent an increasingly popular class of gene delivery vectors . Originating from naturally occurring cell-penetrating sequences and shown to effectively traverse cell membranes, such peptides vary in sequence and amino acid composition, are relatively short, with 20–30 amino acid residues, and can be of different origin including de novo sequences .…”

Section: Introductionmentioning

confidence: 99%

“…Among many chemistries used, cationic amphipathic peptides represent an increasingly popular class of gene delivery vectors. 9 Originating from naturally occurring cell-penetrating sequences and shown to effectively traverse cell membranes, such peptides vary in sequence and amino acid composition, are relatively short, with 20−30 amino acid residues, and can be of different origin including de novo sequences. 10 A significant advantage of the peptides over other nonviral vectors is that their sequences can incorporate specific recognition motifs to exploit virus biology, such as targeting or endosomal escape, and can be modified with nonpeptide motifs including small molecules, aptamers, and antibodies before or after peptide complexation with DNA.…”

Section: ■ Introductionmentioning

confidence: 99%

Folding-Mediated DNA Delivery by α-Helical Amphipathic Peptides

Noble

Vila-Gómez

Rey

et al. 2023

ACS Biomater. Sci. Eng.

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The renaissance gene therapy experiences these days requires specialist biomaterials and a systemic understanding of major factors influencing their ability to deliver genetic material. Peptide transfection systems represent a major class of such biomaterials. Several peptidic reagents have been commercialized to date. However, a comparative assessment of peptide sequences alone without auxiliary support or excipients against a common determinant for their ability to complex and deliver DNA has been lacking. This study cross-compares commercial and experimental transfection reagents from the same family of helical amphiphiles. Factors defining the efficacy of DNA delivery including cell uptake and gene expression are assessed along with cytotoxicity and DNA complexation. The results show 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 cross-comparison revealed that functional DNA delivery is independent of the peptide sequence used but is mediated by the ability of the reagents to co-fold with DNA. Peptide folding proved to be the common determinant for DNA complexation and delivery by peptidic transfection reagents.

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“…Cell penetrating peptides (CPPs) have gained interest in the field of bioengineering given their unique ability to cross the cell membrane for intracellular drug delivery. , NPs modified with CPPs have been reported for increasing internalization in cells for various applications including targeting and imaging of cancer. − NPs are modified with CPPs by two major strategies including electrostatic interaction and covalent crosslinking such as click chemistry. Among CPPs, cationic CPPs such as the transactivator protein (Tat) of human deficiency virus (HIV) are the most frequently used for modifying NPs .…”

Section: Introductionmentioning

confidence: 99%

Supramolecular Peptide Nanofiber/PLGA Nanocomposites for Enhancing Pulmonary Drug Delivery

Chintapula

Yang

Nguyen

et al. 2022

ACS Appl. Mater. Interfaces

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Effective drug delivery to pulmonary sites will benefit from the design and synthesis of novel drug delivery systems that can overcome various tissue and cellular barriers. Cell penetrating peptides (CPPs) have shown promise for intracellular delivery of various imaging probes and therapeutics. Although CPPs improve delivery efficacy to a certain extent, they still lack the scope of engineering to improve the payload capacity and protect the payload from the physiological environment in drug delivery applications. Inspired by recent advances of CPPs and CPPfunctionalized nanoparticles, in this work, we demonstrate a novel nanocomposite consisting of fiber-forming supramolecular CPPs that are coated onto polylactic-glycolic acid (PLGA) nanoparticles to enhance pulmonary drug delivery. These nanocomposites show a threefold higher intracellular delivery of nanoparticles in various cells including primary lung epithelial cells, macrophages, and a 10-fold increase in endothelial cells compared to naked PLGA nanoparticles or a twofold increase compared to nanoparticles modified with traditional monomeric CPPs. Cell uptake studies suggest that nanocomposites likely enter cells through mixed macropinocytosis and passive energy-independent mechanisms, which is followed by endosomal escape within 24 h. Nanocomposites also showed potent mucus permeation. More importantly, freeze-drying and nebulizing formulated nanocomposite powder did not affect their physiochemical and biological activity, which further highlights the translative potential for use as a stable drug carrier for pulmonary drug delivery. We expect nanocomposites based on peptide nanofibers, and PLGA nanoparticles can be custom designed to encapsulate and deliver a wide range of therapeutics including nucleic acids, proteins, and small-molecule drugs when employed in inhalable systems to treat various pulmonary diseases.

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Peptide Nanoparticles for Gene Packaging and Intracellular Delivery

Cited by 7 publications

References 26 publications

Biofoundries are a nucleating hub for industrial translation

Biofoundries are a nucleating hub for industrial translation

Folding-Mediated DNA Delivery by α-Helical Amphipathic Peptides

Supramolecular Peptide Nanofiber/PLGA Nanocomposites for Enhancing Pulmonary Drug Delivery

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