Simplifying the Chemical Structure of Cationic Lipids for siRNA-Lipid Nanoparticles

Kuboyama, Takeshi; Yagi, Kaori; Naoi, Tomoyuki; Era, Tomohiro; Yagi, Nobuhiro; Nakasato, Yoshisuke; Yabuuchi, Hayato; Takahashi, Saori; Shinohara, Fumikazu; Iwai, Hiroto; Koubara-Yamada, Ayumi; Hasegawa, Koki; Miwa, Atsushi

doi:10.1021/acsmedchemlett.8b00652

Cited by 16 publications

(10 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some cationic lipids can also simulate immune response and affect cell signaling pathways ( Vangasseri et al, 2006 ; Lonez et al, 2008 ). The structural design of these lipid materials has the potential to improve the safety application of lipid-based nanoparticles for siRNA delivery, and the doses of both siRNA and lipids should be optimized when applied ( Perrie et al, 2001 ; Niculescu-Duvaz et al, 2003 ; Kuboyama et al, 2019 ; Lin et al, 2019 ; Sato et al, 2019 ).…”

Section: Challenges and Strategiesmentioning

confidence: 99%

Rationale and Application of PEGylated Lipid-Based System for Advanced Target Delivery of siRNA

Chen

Zhao

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

RNA interference (RNAi) technology has become a powerful tool in application of unraveling the mechanism of disease and may hold the potential to be developed for clinical uses. Small interfering RNA (siRNA) can bind to target mRNA with high specificity and efficacy and thus inhibit the expression of related protein for the purpose of treatment of diseases. The major challenge for RNAi application is how to improve its stability and bioactivity and therefore deliver therapeutic agents to the target sites with high efficiency and accuracy. PEGylated lipid-based delivery system has been widely used for development of various medicines due to its long circulating half-life time, low toxicity, biocompatibility, and easiness to be scaled up. The PEGylated lipid-based delivery system may also provide platform for targeting delivery of nucleic acids, and some of the research works have moved to the phases for clinical trials. In this review, we introduced the mechanism, major challenges, and strategies to overcome technical barriers of PEGylated lipid-based delivery systems for advanced target delivery of siRNA in vivo. We also summarized recent advance of PEGylated lipid-based siRNA delivery systems and included some successful research works in this field.

show abstract

Section: Challenges and Strategiesmentioning

confidence: 99%

Rationale and Application of PEGylated Lipid-Based System for Advanced Target Delivery of siRNA

Chen

Zhao

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Gene delivery can be performed using viral [ 14 ] or non-viral [ 15 ] carriers. The first non-viral carriers were linear cationic homopolymers, block-copolymers [ 16 ] and liposomes [ 17 ] based on cationic lipids. Cationic polysaccharides [ 18 ] and cationic peptides [ 19 , 20 ] were also used for this purpose.…”

Section: Introductionmentioning

confidence: 99%

Why the Orientational Mobility in Arginine and Lysine Spacers of Peptide Dendrimers Designed for Gene Delivery Is Different?

Bezrodnyi

Shavykin

Mikhtaniuk

et al. 2020

IJMS

View full text Add to dashboard Cite

New peptide dendrimer with Lys-2Arg repeating units was recently studied experimentally by NMR (RSC Advances, 2019, 9, 18018) and tested as gene carrier successfully (Int. J. Mol. Sci., 2020, 21, 3138). The unusual slowing down of the orientational mobility of 2Arg spacers in this dendrimer was revealed. It has been suggested that this unexpected behavior is caused by the Arg-Arg pairing effect in water, which leads to entanglements between dendrimer branches. In this paper, we determine the reason for this slowing down using atomistic molecular dynamics simulation of this dendrimer. We present that the structural properties of Lys-2Arg dendrimer are close to those of the Lys-2Lys dendrimer at all temperatures (Polymers, 2020, 12, 1657). However, the orientational mobility of the H-H vector in CH2-N groups of 2Arg spacers in Lys-2Arg dendrimer is significantly slower than the mobility of the same vector in the Lys-2Lys dendrimer. This result is in agreement with the recent NMR experiments for the same systems. We revealed that this difference is not due to the arginine-arginine pairing, but is due to the semiflexibility effect associated with the different contour length from CH2-N group to the end of the side arginine or lysine segment in spacers.

show abstract

“…Their high cationic charge also favors efficient endosomal uptake, but this charge also carries some cytotoxicity [10]. In addition, a full understanding of the role components of these polymers play in transfection makes rational design more elusive and makes translation to clinical applications more challenging [33][34][35]. Cationic lipids have also shown some cytotoxicity and have required extensive formulation work to optimize ideal combinations and concentrations of lipid components.…”

Section: Stabilitymentioning

confidence: 99%

Non-Viral Delivery of RNA Gene Therapy to the Central Nervous System

Hauck

Hecker

2022

Pharmaceutics

View full text Add to dashboard Cite

Appropriate gene delivery systems are essential for successful gene therapy in clinical medicine. Lipid-mediated nucleic acid delivery is an alternative to viral vector-mediated gene delivery and has the following advantages. Lipid-mediated delivery of DNA or mRNA is usually more rapid than viral-mediated delivery, offers a larger payload, and has a nearly zero risk of incorporation. Lipid-mediated delivery of DNA or RNA is therefore preferable to viral DNA delivery in those clinical applications that do not require long-term expression for chronic conditions. Delivery of RNA may be preferable to non-viral DNA delivery in some clinical applications, since transit across the nuclear membrane is not necessary, and onset of expression with RNA is therefore even faster than with DNA, although both are faster than most viral vectors. Delivery of RNA to target organ(s) has previously been challenging due to RNA’s rapid degradation in biological systems, but cationic lipids complexed with RNA, as well as lipid nanoparticles (LNPs), have allowed for delivery and expression of the complexed RNA both in vitro and in vivo. This review will focus on the non-viral lipid-mediated delivery of RNAs, including mRNA, siRNA, shRNA, and microRNA, to the central nervous system (CNS), an organ with at least two unique challenges. The CNS contains a large number of slowly dividing or non-dividing cell types and is protected by the blood brain barrier (BBB). In non-dividing cells, RNA-lipid complexes demonstrated increased transfection efficiency relative to DNA transfection. The efficiency, timing of the onset, and duration of expression after transfection may determine which nucleic acid is best for which proposed therapy. Expression can be seen as soon as 1 h after RNA delivery, but duration of expression has been limited to 5–7 h. In contrast, transfection with a DNA lipoplex demonstrates protein expression within 5 h and lasts as long as several weeks after transfection.

show abstract

Simplifying the Chemical Structure of Cationic Lipids for siRNA-Lipid Nanoparticles

Cited by 16 publications

References 23 publications

Rationale and Application of PEGylated Lipid-Based System for Advanced Target Delivery of siRNA

Rationale and Application of PEGylated Lipid-Based System for Advanced Target Delivery of siRNA

Why the Orientational Mobility in Arginine and Lysine Spacers of Peptide Dendrimers Designed for Gene Delivery Is Different?

Non-Viral Delivery of RNA Gene Therapy to the Central Nervous System

Contact Info

Product

Resources

About