Incorporation of phosphatidylserine improves efficiency of lipid based gene delivery systems

Claudia, Lotter,; Alter, Claudio Luca; Bolten, Jan Stephan; Detampel, Pascal; Palivan, Cornelia G.; Einfalt, Tomaz; Huwyler, Jörg

doi:10.1016/j.ejpb.2022.02.007

Cited by 21 publications

(19 citation statements)

References 51 publications

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“…(D) Illustrates the design of PS-LNPs inspired by viral membrane lipids and provides an overview of methods to evaluate their ability to deliver RNA. (Adapted with permission under a Creative Commons CC-BY License from ref ( 111 ). Copyright 2022, Elsevier.)…”

Section: Bioinspired Lipid-based Nanocarriersmentioning

confidence: 99%

“… 111 , 169 In mammalian cells, PS is naturally contained within the cell membrane; however, once these cells undergo apoptosis or necrosis, PS is exposed outside the cell membrane. 111 This process induces PS recognition, causing apoptotic clearance. In viruses, PS found on the outer viral membrane disguises it as an apoptotic body and causes cells (including macrophages and tissue cells) to engulf virions through cell clearance mechanisms.…”

Section: Bioinspired Lipid-based Nanocarriersmentioning

confidence: 99%

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Bioinspired Lipid Nanocarriers for RNA Delivery

Golubovic

Tsai

2023

ACS Bio Med Chem Au

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RNA therapy is a disruptive technology comprising a rapidly expanding category of drugs. Further translation of RNA therapies to the clinic will improve the treatment of many diseases and help enable personalized medicine. However, in vivo delivery of RNA remains challenging due to the lack of appropriate delivery tools. Current state-of-the-art carriers such as ionizable lipid nanoparticles still face significant challenges, including frequent localization to clearance-associated organs and limited (1–2%) endosomal escape. Thus, delivery vehicles must be improved to further unlock the full potential of RNA therapeutics. An emerging strategy is to modify existing or new lipid nanocarriers by incorporating bioinspired design principles. This method generally aims to improve tissue targeting, cellular uptake, and endosomal escape, addressing some of the critical issues facing the field. In this review, we introduce the different strategies for creating bioinspired lipid-based RNA carriers and discuss the potential implications of each strategy based on reported findings. These strategies include incorporating naturally derived lipids into existing nanocarriers and mimicking bioderived molecules, viruses, and exosomes. We evaluate each strategy based on the critical factors required for delivery vehicles to succeed. Finally, we point to areas of research that should be furthered to enable the more successful rational design of lipid nanocarriers for RNA delivery.

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Section: Bioinspired Lipid-based Nanocarriersmentioning

confidence: 99%

Section: Bioinspired Lipid-based Nanocarriersmentioning

confidence: 99%

Bioinspired Lipid Nanocarriers for RNA Delivery

Golubovic

Tsai

2023

ACS Bio Med Chem Au

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“…Pfizer and Moderna vaccines were designed to "imitate" dying cells or apoptotic bodies by utilizing ionizable lipids and DSPC delivering mRNA directly to the immune cells' translation machinery [5]. However, DSPC's resemblance to PS may inadvertently activate ADAM 10 and 17, promoting pathological cell-cell fusion and subsequent pathology [40].…”

Section: Dspc and Ionizable Lipidsmentioning

confidence: 99%

“…The LNP transfection likely involves particle engulfment by the host immune cells due to their resemblance to apoptotic bodies, vesicles with externalized phosphatidylserine (ePS). As the LNPs are decorated with PSlike ionizable phospholipids, including 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), they encourage human phagocytes into internalizing them [4][5][6].…”

mentioning

confidence: 99%

COVID-19 mRNA vaccines and pathological cell-cell fusion: an unintended consequence

Sfera¹,

Thomas²,

Sfera³

et al. 2022

Arch Clin Trials

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“…The LNP transfection likely involves particle engulfment by the host immune cells due to their resemblance to apoptotic bodies, vesicles with externalized phosphatidylserine (ePS). As the LNPs are decorated with PS-like ionizable phospholipids, including 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), they encourage human phagocytes into internalizing them [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Do Messenger RNA Vaccines Induce Pathological Syncytia?

Adonis¹,

G²,

O³

et al. 2022

Int J Pathol Clin Res

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subcellular structures [13]. The development of such therapeutics is anticipated to redefine clinical pathways, including for non-communicable diseases. However, are these therapies ready for worldwide application in their present molecular form?The question has been asked before, often in relation to the potential toxicity of lipid formulations used in the past, especially as part of the delivering cancer therapeutics [14,15]. However, in the following sections, we take a closer look at a novel perspective, namely the mRNA vaccines' structure and composition and at their unintended biological consequences derived from pathological cell-cell fusion. Messenger RNA Vaccines, an OverviewTo elicit the formation of neutralizing antibodies, exogenously administered mRNA must avoid two key obstacles: Hydrolysis by extracellular RNAases and recognition by cytosolic innate immune sensors, including toll-like receptors (TLRs) and retinoic acidinducible gene I (RIG-I) protein [16,17]. The former is accomplished by hiding the nucleic acid backbone into LNPs, while the latter by attaching nucleobases, such as N1-methylpseudouridine (m1Ψ) to the mRNA [18,19] (Figure 1). The coding region of the mRNA is flanked by two untranslated regions (UTRs) followed by a polyadenylated (polyA) tail at 3' and a cap at 5' for

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Incorporation of phosphatidylserine improves efficiency of lipid based gene delivery systems

Cited by 21 publications

References 51 publications

Bioinspired Lipid Nanocarriers for RNA Delivery

Bioinspired Lipid Nanocarriers for RNA Delivery

COVID-19 mRNA vaccines and pathological cell-cell fusion: an unintended consequence

Do Messenger RNA Vaccines Induce Pathological Syncytia?

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