Polymeric and lipid nanoparticles for delivery of self-amplifying RNA vaccines

Blakney, Anna K.; McKay, Paul F.; Hu, Kai; Samnuan, Karnyart; Jain, Nikita; Brown, Andrew F.; Thomas, Anitha; Rogers, P. S. Z.; Polra, Krunal; Sallah, Hadijatou; Yeow, Jonathan; Zhu, Yunqing; Stevens, Molly M.; Geall, Andrew J.; Shattock, Robin J.

doi:10.1016/j.jconrel.2021.08.029

Cited by 80 publications

(76 citation statements)

References 27 publications

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Section: Gene Deliverymentioning

confidence: 99%

“…Currently, lipid-based nanoparticles (LNPs) are the most clinically progressed nanoplatforms for delivering nucleic acids. Nonetheless, Blakney et al [275] have compared the efficiency of LNP to that of pABOL bioreducible polymer in self-amplifying RNA (saRNA) delivery. Both tested platforms induced enhanced levels of IFN-γ, IL-12, IL-5, and TNF-α 4 h after administration.…”

Section: Gene Deliverymentioning

confidence: 99%

“…Moreover, the virus can be regarded as a functional nanomaterial, due to its nanometric size and core-shell nanostructure [340,341]. Thus, various nanoplatforms, such as lipid nanoparticles, polyplexes, dendrimers, cationic polysaccharide particles, and cationic nanoemulsions, were tested for delivering nucleic acids in vaccine formulations [17,275,338,342]. Out of the plethora of possibilities, lipid nanoparticles (LNP) are the most clinically advanced, both Pfizer/BioNTech and Moderna COVID-19 vaccines being LNP formulations [17,275].…”

Section: Covid-19 Immunizationmentioning

confidence: 99%

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Polymer-Based Nanosystems—A Versatile Delivery Approach

Niculescu

Grumezescu

2021

Materials

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Polymer-based nanoparticles of tailored size, morphology, and surface properties have attracted increasing attention as carriers for drugs, biomolecules, and genes. By protecting the payload from degradation and maintaining sustained and controlled release of the drug, polymeric nanoparticles can reduce drug clearance, increase their cargo’s stability and solubility, prolong its half-life, and ensure optimal concentration at the target site. The inherent immunomodulatory properties of specific polymer nanoparticles, coupled with their drug encapsulation ability, have raised particular interest in vaccine delivery. This paper aims to review current and emerging drug delivery applications of both branched and linear, natural, and synthetic polymer nanostructures, focusing on their role in vaccine development.

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Section: Gene Deliverymentioning

confidence: 99%

Section: Gene Deliverymentioning

confidence: 99%

Section: Covid-19 Immunizationmentioning

confidence: 99%

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Polymer-Based Nanosystems—A Versatile Delivery Approach

Niculescu

Grumezescu

2021

Materials

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“…13 − 15 To circumvent these challenges, biomaterials researchers have designed chemically defined synthetic delivery platforms such as polymers 16 and lipids 17 whose performance meets or exceeds benchmarks set by clinically deployed viral vectors. 18 , 19 …”

Section: Introductionmentioning

confidence: 99%

Combinatorial Polycation Synthesis and Causal Machine Learning Reveal Divergent Polymer Design Rules for Effective pDNA and Ribonucleoprotein Delivery

Kumar

Oviedo³

et al. 2022

JACS Au

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The development of polymers that can replace engineered viral vectors in clinical gene therapy has proven elusive despite the vast portfolios of multifunctional polymers generated by advances in polymer synthesis. Functional delivery of payloads such as plasmids (pDNA) and ribonucleoproteins (RNP) to various cellular populations and tissue types requires design precision. Herein, we systematically screen a combinatorially designed library of 43 well-defined polymers, ultimately identifying a lead polycationic vehicle (P38) for efficient pDNA delivery. Further, we demonstrate the versatility of P38 in codelivering spCas9 RNP and pDNA payloads to mediate homology-directed repair as well as in facilitating efficient pDNA delivery in ARPE-19 cells. P38 achieves nuclear import of pDNA and eludes lysosomal processing far more effectively than a structural analogue that does not deliver pDNA as efficiently. To reveal the physicochemical drivers of P38’s gene delivery performance, SHapley Additive exPlanations (SHAP) are computed for nine polyplex features, and a causal model is applied to evaluate the average treatment effect of the most important features selected by SHAP. Our machine learning interpretability and causal inference approach derives structure–function relationships underlying delivery efficiency, polyplex uptake, and cellular viability and probes the overlap in polymer design criteria between RNP and pDNA payloads. Together, combinatorial polymer synthesis, parallelized biological screening, and machine learning establish that pDNA delivery demands careful tuning of polycation protonation equilibria while RNP payloads are delivered most efficaciously by polymers that deprotonate cooperatively via hydrophobic interactions. These payload-specific design guidelines will inform further design of bespoke polymers for specific therapeutic contexts.

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“…The recent investigation of a multitude of therapeutic nucleic acids (TNAs) has paved the way for developing new treatment strategies for various wounds, infectious diseases, and chronic conditions. TNAs, such as plasmid DNA (pDNA), small interfering (or silencing) RNA (siRNA), self-amplifying RNA (saRNA), microRNA mimics, anti-microRNA oligonucleotides, messenger RNA (mRNA), and antisense oligonucleotides (ASOs), can be employed for creating therapeutics and vaccines that provide a cell-mediated immune response [1][2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

New Applications of Lipid and Polymer-Based Nanoparticles for Nucleic Acids Delivery

2021

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Nucleic acids represent a promising lead for engineering the immune system. However, naked DNA, mRNA, siRNA, and other nucleic acids are prone to enzymatic degradation and face challenges crossing the cell membrane. Therefore, increasing research has been recently focused on developing novel delivery systems that are able to overcome these drawbacks. Particular attention has been drawn to designing lipid and polymer-based nanoparticles that protect nucleic acids and ensure their targeted delivery, controlled release, and enhanced cellular uptake. In this respect, this review aims to present the recent advances in the field, highlighting the possibility of using these nanosystems for therapeutic and prophylactic purposes towards combatting a broad range of infectious, chronic, and genetic disorders.

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Polymeric and lipid nanoparticles for delivery of self-amplifying RNA vaccines

Cited by 80 publications

References 27 publications

Polymer-Based Nanosystems—A Versatile Delivery Approach

Polymer-Based Nanosystems—A Versatile Delivery Approach

Combinatorial Polycation Synthesis and Causal Machine Learning Reveal Divergent Polymer Design Rules for Effective pDNA and Ribonucleoprotein Delivery

New Applications of Lipid and Polymer-Based Nanoparticles for Nucleic Acids Delivery

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