Single-Tailed Lipidoids Enhance the Transfection Activity of Their Double-Tailed Counterparts

Wu, Yihang; Li, Linxian; Chen, Qing; Su, Yi; Levkin, Pavel A.; Davidson, Gary

doi:10.1021/acscombsci.5b00117

Cited by 10 publications

(8 citation statements)

References 31 publications

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“…Lipid-like molecules that are substituted with only one tail result in poor efficiency compared to their bi-tailed counterparts. However, a synergistic effect could be observed when mixing mono- and bi-tailed lipids at different ratios. , Monotailed lipids increase the surface charge, whereas bi-tailed lipids decrease lipid nanoparticle size and increase stability . In the field of lipidoid synthesis, attachment of more than two alkyl tails is considered to be very important to promote high gene delivery efficiencies. , …”

Section: Lipid-based Dna Delivery Systemsmentioning

confidence: 99%

Lipid-Based DNA Therapeutics: Hallmarks of Non-Viral Gene Delivery

et al. 2019

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Gene therapy is a promising strategy for the treatment of monogenic disorders. Non-viral gene delivery systems including lipid-based DNA therapeutics offer the opportunity to deliver an encoding gene sequence specifically to the target tissue and thus enable the expression of therapeutic proteins in diseased cells. Currently, available gene delivery approaches based on DNA are inefficient and require improvements to achieve clinical utility. In this Review, we discuss state-of-the-art lipid-based DNA delivery systems that have been investigated in a preclinical setting. We emphasize factors influencing the delivery and subsequent gene expression in vitro, ex vivo, and in vivo. In addition, we cover aspects of nanoparticle engineering and optimization for DNA therapeutics. Finally, we highlight achievements of lipid-based DNA therapies in clinical trials.

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Section: Lipid-based Dna Delivery Systemsmentioning

confidence: 99%

Lipid-Based DNA Therapeutics: Hallmarks of Non-Viral Gene Delivery

et al. 2019

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“… 9 , 25 , 26 , 27 It has been reported that TE is highly correlated with nanoparticle size and surface charge, both of which are affected by lipid composition. 28 , 29 Additionally, the active targeting and appropriate characteristics of CLs can also be obtained by simply tailoring the lipid compositions, which are crucial to the outperformance of CLs in the body. Therefore, the rational design of CLs requires a full understanding of the relationship between lipid composition and therapeutic outcome.…”

Section: Main Textmentioning

confidence: 99%

Barriers and Strategies of Cationic Liposomes for Cancer Gene Therapy

Liu

Zhang

Zhu

et al. 2020

Molecular Therapy - Methods & Clinical Development

147

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Cationic liposomes (CLs) have been regarded as the most promising gene delivery vectors for decades with the advantages of excellent biodegradability, biocompatibility, and high nucleic acid encapsulation efficiency. However, the clinical use of CLs in cancer gene therapy is limited because of many uncertain factors in vivo . Extracellular barriers such as opsonization, rapid clearance by the reticuloendothelial system and poor tumor penetration, and intracellular barriers, including endosomal/lysosomal entrapped network and restricted diffusion to the nucleus, make CLs not the ideal vector for transferring extrinsic genes in the body. However, the obstacles in achieving productive therapeutic effects of nucleic acids can be addressed by tailoring the properties of CLs, which are influenced by lipid compositions and surface modification. This review focuses on the physiological barriers of CLs against cancer gene therapy and the effects of lipid compositions on governing transfection efficiency, and it briefly discusses the impacts of particle size, membrane charge density, and surface modification on the fate of CLs in vivo , which may provide guidance for their preclinical studies.

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“…By contrast, single-chained cationic lipids are more prone to form unstable lipoplexes characterized by higher cytotoxicity and reduced transfection efficiency (Lv et al, 2006;Pinnaduwage et al, 1989). Of note, the combination of single-and doubletailed lipids to give mixed liposomes had a positive synergistic effect on the transfection efficiency (Li et al, 2013;Wu et al, 2016).…”

Section: Aliphatic Chainsmentioning

confidence: 99%

Cationic lipids for gene delivery: many players, one goal

Ponti

Campolungo

Melchiori

et al. 2021

Chemistry and Physics of Lipids

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Lipid-based carriers represent the most widely used alternative to viral vectors for gene expression and gene silencing purposes. This class of non-viral vectors is particularly attractive for their ease of synthesis and chemical modifications to endow them with desirable properties. Despite combinatorial approaches have led to the generation of a large number of cationic lipids displaying different supramolecular structures and improved behavior, additional efforts are needed towards the development of more and more effective cationic lipids for transfection purposes. With this review, we seek to highlight the great progress made in the design of each and every constituent domain of cationic lipids, that is, the chemical structure of the headgroup, linker and hydrophobic moieties, and on the specific effect on the assembly with nucleic acids. Since the complexity of such systems is known to affect their performances, the role of formulation, stability and phase behavior on the transfection efficiency of such assemblies will be thoroughly discussed. Our objective is to provide a conceptual framework for the development of ever more performing lipid gene delivery vectors. Highlights: Progress in the rational design of cationic lipids  Outlook on the influence of cationic lipid domains on nucleic acids complexation and delivery  Outlook on the influence of cationic lipid composition on its ultimate geometry and supramolecular structures of lipoplexes Abbreviations:

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Single-Tailed Lipidoids Enhance the Transfection Activity of Their Double-Tailed Counterparts

Cited by 10 publications

References 31 publications

Lipid-Based DNA Therapeutics: Hallmarks of Non-Viral Gene Delivery

Lipid-Based DNA Therapeutics: Hallmarks of Non-Viral Gene Delivery

Barriers and Strategies of Cationic Liposomes for Cancer Gene Therapy

Cationic lipids for gene delivery: many players, one goal

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