Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection

Ma, Feihe; Yang, Liu; Sun, Zhuorui; Chen, Jinjin; Rui, Xuehui; Glass, Zachary; Xu, Qiaobing

doi:10.1126/sciadv.abb4429

Cited by 96 publications

(91 citation statements)

References 37 publications

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“…Alternatively, biomimetic lipids can be designed to achieve organ-targeted delivery. For example, neurotransmitters are endogenous chemicals that can cross the blood–brain barrier and participate in neurotransmission 82 . Thus, neurotransmitter-derived lipids can be used for mRNA delivery to the brain following i.v.…”

Section: Discussionmentioning

confidence: 99%

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Lipid nanoparticles for mRNA delivery

et al. 2021

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Messenger RNA (mRNA) has emerged as a new category of therapeutic agent to prevent and treat various diseases. To function in vivo, mRNA requires safe, effective and stable delivery systems that protect the nucleic acid from degradation and that allow cellular uptake and mRNA release. Lipid nanoparticles have successfully entered the clinic for the delivery of mRNA; in particular, lipid nanoparticle–mRNA vaccines are now in clinical use against coronavirus disease 2019 (COVID-19), which marks a milestone for mRNA therapeutics. In this Review, we discuss the design of lipid nanoparticles for mRNA delivery and examine physiological barriers and possible administration routes for lipid nanoparticle–mRNA systems. We then consider key points for the clinical translation of lipid nanoparticle–mRNA formulations, including good manufacturing practice, stability, storage and safety, and highlight preclinical and clinical studies of lipid nanoparticle–mRNA therapeutics for infectious diseases, cancer and genetic disorders. Finally, we give an outlook to future possibilities and remaining challenges for this promising technology.

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Section: Discussionmentioning

confidence: 99%

“…Thus, neurotransmitter-derived lipids can be used for mRNA delivery to the brain following i.v. injection 82 . Testing and comparing the cell distribution of many different lipid nanoparticle formulations remains challenging.…”

Section: Discussionmentioning

confidence: 99%

Lipid nanoparticles for mRNA delivery

et al. 2021

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“…As tryptamine has been shown to effectively cross the BBB via active transport, Ma et al designed tryptamine-conjugated lipidoids (NT1-lipidoids) with 14 carbons in the aliphatic tail chain mixed into BBB-impermeable lipid nanoparticles (306-O12–3) containing a PEGylated lipid DSPE-PEG2000 ( Ma et al, 2020 ). This particle was used to deliver an anti-tau PS 2MOE ASO gapmer through tail vein injection in mice.…”

Section: Innovation In Nucleic Acid–based Therapeutics Chemistrymentioning

confidence: 99%

Nucleic Acid–Based Therapeutics in Orphan Neurological Disorders: Recent Developments

Khorkova

Hsiao

Wahlestedt

2021

Front. Mol. Biosci.

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The possibility of rational design and the resulting faster and more cost-efficient development cycles of nucleic acid–based therapeutics (NBTs), such as antisense oligonucleotides, siRNAs, and gene therapy vectors, have fueled increased activity in developing therapies for orphan diseases. Despite the difficulty of delivering NBTs beyond the blood–brain barrier, neurological diseases are significantly represented among the first targets for NBTs. As orphan disease NBTs are now entering the clinical stage, substantial efforts are required to develop the scientific background and infrastructure for NBT design and mechanistic studies, genetic testing, understanding natural history of orphan disorders, data sharing, NBT manufacturing, and regulatory support. The outcomes of these efforts will also benefit patients with “common” diseases by improving diagnostics, developing the widely applicable NBT technology platforms, and promoting deeper understanding of biological mechanisms that underlie disease pathogenesis. Furthermore, with successes in genetic research, a growing proportion of “common” disease cases can now be attributed to mutations in particular genes, essentially extending the orphan disease field. Together, the developments occurring in orphan diseases are building the foundation for the future of personalized medicine. In this review, we will focus on recent achievements in developing therapies for orphan neurological disorders.

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“…Similar to the Aβ‐targeted therapy, inhibition of tau production is also beneficial to reduce the NFTs burden in the AD brain. For instance, neurotransmitter‐derived lipidoids (NT‐lipidoids) loaded with antisense oligonucleotides were reported can efficiently reduce approximately 50% of tau expression in the brain of AD mouse (Ma et al, 2020). However, the nonspecific silencing of tau protein may also bring safety hazards, because it is also distributed throughout the body and has important physiological functions.…”

Section: Ad Therapy Using Functional Nanoassembliesmentioning

confidence: 99%

Functional nanoassemblies for the diagnosis and therapy of Alzheimer's diseases

Zhang

Sun

Chen

et al. 2021

WIREs Nanomed Nanobiotechnol

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Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects populations around the world. Many therapeutics have been investigated for AD diagnosis and/or therapy, but the efficacy is largely limited by the poor bioavailability of drugs and by the presence of the blood–brain barrier. Recently, the development of nanomedicines enables efficient drug delivery to the brain, but the complex pathological mechanism of AD prevents them from successful treatment. As a type of advanced nanomedicine, multifunctional nanoassemblies self‐assembled from nanoscale imaging or therapeutic agents can simultaneously target multiple pathological factors, showing great potential in the diagnosis and therapy of AD. To help readers better understand this emerging field, in this review, we first introduce the pathological mechanisms and the potential drug candidates of AD, as well as the design strategies of nanoassemblies for improving AD targeting efficiency. Moreover, the progress of dynamic nanoassemblies that can diagnose and/or treat AD in response to the endogenous or exogenous stimuli will be described. Finally, we conclude with our perspectives on the future development in this field. The objective of this review is to outline the latest progress of using nanoassemblies to overcome the complex pathological environment of AD for improved diagnosis and therapy, in hopes of accelerating the future development of intelligent AD nanomedicines. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging

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Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection

Cited by 96 publications

References 37 publications

Lipid nanoparticles for mRNA delivery

Lipid nanoparticles for mRNA delivery

Nucleic Acid–Based Therapeutics in Orphan Neurological Disorders: Recent Developments

Functional nanoassemblies for the diagnosis and therapy of Alzheimer's diseases

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