Ionizable Lipid Nanoparticle-Mediated Delivery of Plasmid DNA in Cardiomyocytes

Scalzo, Sérgio; Santos, Anderson K.; Ferreira, Heloisa Aparecida; Costa, P.A.C.R.; Prazeres, Pedro H. D. M.; Silva, Natália Jordana Alves da; Guimarães, Lays Cordeiro; Silva, Mário de Morais E; Alves, Marco Túllio R.; Viana, Celso Tarso Rodrigues; Jesus, Itamar Couto Guedes de; Rodrigues, Alice P; Birbrair, Alexander; Lobo, Anderson Oliveira; Frézard, Frédéric; Mitchell, Michael J.; Guatimosim, Sílvia; Guimarães, Pedro Pires Goulart

doi:10.2147/ijn.s366962

Cited by 25 publications

(21 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, Pedro Pires and colleagues demonstrated the potential of LNPs in delivering pDNA to cardiomyocytes through screening and optimizing lipid libraries. 101 They created a mini-library of engineered LNPs and optimized the lipid ratio to eventually select LNP4, which exhibited the highest green fluorescent protein (GFP) expression in cardiomyocytes in vitro , superior heart transfection efficacy in vivo and reduced toxicity. They proposed that the formulation’s high DOPE and low cholesterol molar ratio in LNP4 may enhance nucleic acids delivery to myocardial cells both in vitro and in vivo .…”

Section: Organ-selective Lnps As Delivery Platforms For Nucleic Acidsmentioning

confidence: 99%

Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo

Zhang,

Yin,

et al. 2024

iScience

View full text Add to dashboard Cite

Section: Organ-selective Lnps As Delivery Platforms For Nucleic Acidsmentioning

confidence: 99%

Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo

Zhang,

Yin,

et al. 2024

iScience

View full text Add to dashboard Cite

“…Such strategies include altering their lipid composition and conjugating tissue-specific receptors ( Cheng et al, 2020 ; Paunovska et al, 2022 ; Dilliard et al, 2021 ; Godbout and Tremblay, 2022 ). For example, Scalzo et al (2022) tested multiple mixtures of LNP formulations to successfully transfect cardiomyocytes in vitro , the best formulation of which subsequently successfully delivered plasmid DNA encoding GFP to the murine heart in vivo upon tail vein injection. To our knowledge, cardiomyocyte-specific targeting has not yet been achieved.…”

Section: Efficiently Delivering Gene Editing Tools To the Heartmentioning

confidence: 99%

Gene editing innovations and their applications in cardiomyopathy research

Kyriakopoulou,

Monnikhof,

van Rooij

2023

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Cardiomyopathies are among the major triggers of heart failure, but their clinical and genetic complexity have hampered our understanding of these disorders and delayed the development of effective treatments. Alongside the recent identification of multiple cardiomyopathy-associated genetic variants, advances in genome editing are providing new opportunities for cardiac disease modeling and therapeutic intervention, both in vitro and in vivo. Two recent innovations in this field, prime and base editors, have improved editing precision and efficiency, and are opening up new possibilities for gene editing of postmitotic tissues, such as the heart. Here, we review recent advances in prime and base editors, the methods to optimize their delivery and targeting efficiency, their strengths and limitations, and the challenges that remain to be addressed to improve the application of these tools to the heart and their translation to the clinic.

show abstract

“…More speci cally, DNA loaded nanocarriers must translocate to the nucleus of the cells to achieve target protein expression (2). Lipid based nanocarriers have therefore been extensively developed to entrap DNA for its safe delivery and high transfection e ciency, ensuring stability, longer circulation, and avoiding renal clearance from the systemic circulation via PEGylation (3). Cationic or ionizable lipid-DNA complexation based lipoplexes have been broadly utilized as DNA delivery systems by employing cationic or ionizable lipids to allow an easy complexation with negatively charged plasmid DNA (pDNA).…”

Section: Introductionmentioning

confidence: 99%

Delineating effect of cationic head group and preparation method on transfection versus toxicity of lipid-based nanoparticles for gene delivery

Saraswat¹,

Patel²

2023

Preprint

View full text Add to dashboard Cite

Gene therapy using plasmid DNA (pDNA) is well-explored for variety of genetic diseases. However, its susceptibility to enzymatic degradation desires an optimal delivery system for efficient cellular uptake, transfection, and stability in vivo. Non-viral vectors like lipoplexes and LNPs have gained traction but there is no comparative evaluation of these lipid nanocarriers to deliver pDNA. Here, we demonstrated parallel comparison of both formulation components and technology for proficient pDNA delivery. Cationic and ionizable head groups were screened to find balance between acceptable transfection efficiency and systemic safety to deliver GFP-pDNA. We observed that lipoplexes formulated using SM-102 as biodegradable ionizable lipid exhibited high transfection efficiency given their high cellular uptake in A375V cells. Ionizable LNPs were fabricated via microfluidics and systematic comparison of lipid nanocarrier with GFP-pDNA complexed on interior versus exterior of nanoparticles was executed. We found LNPs to unveil high transfection efficiency and penetration within 3D spheroid model, while protecting pDNA under simulated physiological conditions. Our study lays a foundation to opt for the right complexing lipid and technology for development of lipid nanocarriers. Taken together, our research has opened the doors to designing “state-of-the-art” LNP based therapies by entrapping any functional plasmid gene that target life-threatening ailments.

show abstract

Ionizable Lipid Nanoparticle-Mediated Delivery of Plasmid DNA in Cardiomyocytes

Cited by 25 publications

References 53 publications

Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo

Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo

Gene editing innovations and their applications in cardiomyopathy research

Delineating effect of cationic head group and preparation method on transfection versus toxicity of lipid-based nanoparticles for gene delivery

Contact Info

Product

Resources

About