Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology, Год журнала: 2024, Номер 18(4), С. 313 - 323
Опубликована: Дек. 1, 2024
Язык: Английский
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 10166 - 10166
Опубликована: Сен. 22, 2024
Lipid nanoparticles (LNPs) have emerged as leading non-viral carriers for messenger RNA (mRNA) delivery in clinical applications. Overcoming challenges safe and effective mRNA to target tissues cells, along with controlling release from the vehicle, remains pivotal mRNA-based therapies. This review elucidates structure of LNPs, mechanism delivery, targeted LNPs various cells tissues, including leukocytes, T-cells, dendritic Kupffer hepatic endothelial extrahepatic tissues. Here, we discuss applications mRNA-LNP vaccines prevention infectious diseases treatment cancer genetic diseases. Although remain terms efficiency, specific tissue targeting, toxicity, storage stability, technology holds extensive potential
Язык: Английский
Процитировано
19
Current Opinion in Chemical Biology, Год журнала: 2024, Номер 81, С. 102506 - 102506
Опубликована: Авг. 1, 2024
Despite impressive recent establishment of therapeutic nucleic acids as drugs and vaccines, their broader medical use is impaired by modest performance in intracellular delivery. Inefficient endosomal escape presents a major limitation responsible for inadequate cytosolic cargo release. Depending on the carrier, this barrier can strongly limit or even abolish acid Different strategies hypothesized mechanisms are reviewed.
Язык: Английский
Процитировано
15
Small, Год журнала: 2024, Номер 20(42)
Опубликована: Июнь 25, 2024
Although small-interfering RNAs (siRNAs) are specific silencers for numerous disease-related genes, their clinical applications still require safe and effective means of delivery into target cells. Highly efficient lipid nanoparticles (LNPs) developed siRNA delivery, showcasing the advantages novel pH-responsive lipoamino xenopeptide (XP) carriers. These sequence-defined XPs assembled by branched lysine linkages between cationizable polar succinoyl tetraethylene pentamine (Stp) units apolar fatty acids (LAFs) at various ratios bundle or U-shape topologies. Formulation siRNA-LNPs using LAF
Язык: Английский
Процитировано
9
Journal of Controlled Release, Год журнала: 2024, Номер 370, С. 239 - 255
Опубликована: Апрель 27, 2024
Double pH-responsive xenopeptide carriers containing succinoyl tetraethylene pentamine (Stp) and lipo amino fatty acids (LAFs) were evaluated for CRISPR/Cas9 based genome editing. Different carrier topologies, variation of LAF/Stp ratios LAF types as Cas9 mRNA/sgRNA polyplexes screened in three different reporter cell lines using genomic targets (Pcsk9, eGFP, mdx exon 23). One U-shaped bundle (B2)-shaped lipo-xenopeptides exhibiting remarkable efficiencies identified. Genome editing potency top observed at sub-nanomolar EC
Язык: Английский
Процитировано
5
European Journal of Pharmaceutical Sciences, Год журнала: 2024, Номер 205, С. 106983 - 106983
Опубликована: Дек. 7, 2024
Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated (Cas) protein has been proved as a powerful tool for the treatment of genetic diseases. The Cas9 protein, when combined with single-guide RNA (sgRNA), forms Cas9/sgRNA ribonucleoprotein (RNP) capable targeting and editing genome. However, limited availability effective carriers restricted broader application CRISPR/Cas9 RNP. In this study, we evaluated dual pH-responsive amphiphilic xenopeptides (XPs) delivering These artificial lipo-XPs contain apolar cationizable lipoamino fatty acid (LAF) polar oligoaminoethylene units such succinoyl-tetraethylenepentamine (Stp) in various ratios U-shaped topologies. were screened functional RNP delivery four different reporter cell lines, including Duchenne muscular dystrophy (DMD) exon skipping model. Significantly enhanced cellular uptake into HeLa cells, endosomal disruption gal8-mRuby3 potent genome by several complexes was observed lines 5 nM sgRNA range. Comparing mRNA/sgRNA polyplexes DMD model demonstrated similar splice site high two molecular modalities. Based on these studies, analogues U1 LAF2-Stp LAF4-Stp2 structures deployed, tuning amphiphilicity Stp group replacement six oligoamino acids dmGtp, chGtp, dGtp, Htp, Stt, or GEIPA. most (containing chGtp GEIPA) further gene efficiency EC50 values 1 line. Notably, LAF2-dGtp reached 0.51 even upon serum incubation. Another carrier (LAF4-GEIPA2) complexing donor DNA, facilitated up to 43 % homology-directed repair (HDR) eGFPd2 cells visualized switch from green fluorescent (eGFP) blue (BFP). This study presents system tunable RNP/donor DNA polyplexes, offering an easily applicable strategy editing.
Язык: Английский
Процитировано
4
ACS Nano, Год журнала: 2024, Номер 18(33), С. 22181 - 22193
Опубликована: Авг. 6, 2024
Nanoparticle-mediated mRNA delivery has emerged as a promising therapeutic modality, but its growth is still limited by the discovery and optimization of effective well-tolerated strategies. Lipid nanoparticles containing charged or ionizable lipids are an emerging standard for in vivo delivery, so creating facile, tunable strategies to synthesize these key lipid-like molecules essential advance field. Here, we generate library N-substituted glycine oligomers, peptoids, undertake multistage down-selection process identify lead candidate peptoids component our Nutshell nanoparticle platform. First, peptoid structural motif clustering >200 based on predicted physical properties evaluate members each cluster reporter gene expression vivo. Then, optimized using design experiments methodology explore variations lipophilic portions peptoid, facilitating trends between elements properties. We further demonstrate that peptoid-based Nutshells leads therapeutically relevant levels anti-respiratory syncytial virus antibody mice with minimal tolerability concerns induced immune responses compared benchmark lipid, DLin-MC3-DMA. Through this work, present platform can be toward range programs.
Язык: Английский
Процитировано
3
Microbial Biotechnology, Год журнала: 2024, Номер 17(11)
Опубликована: Ноя. 1, 2024
Abstract Despite the great potential of DNA vaccines for a broad range applications, ranging from prevention infections, over treatment autoimmune and allergic diseases to cancer immunotherapies, implementation such therapies clinical is far behind expectations up now. The main reason poor immunogenicity in humans. Consequently, improvement performance vivo required. This mini‐review provides an overview current state various strategies enhance immunogenic vaccines, including (i) optimization construct itself regarding size, nuclear transfer transcriptional regulation; (ii) use appropriate adjuvants; (iii) improved delivery, example, by careful choice administration route, physical methods as electroporation nanomaterials that may allow cell type‐specific targeting. Moreover, combining nanoformulated with other immunotherapies prime‐boost help success treatment.
Язык: Английский
Процитировано
2
Nanoscale, Год журнала: 2024, Номер 16(29), С. 13988 - 14005
Опубликована: Янв. 1, 2024
Double pH-responsive xenopeptides comprising polar ionizable succinoyl tetraethylene pentamine (Stp) motifs and lipophilic lipoamino fatty acids (LAFs) were recently found to efficiently transfect mRNA pDNA at low doses.
Язык: Английский
Процитировано
0
Биологические мембраны Журнал мембранной и клеточной биологии, Год журнала: 2024, Номер 41(4), С. 309 - 321
Опубликована: Ноя. 3, 2024
Язык: Английский
Процитировано
0
Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology, Год журнала: 2024, Номер 18(4), С. 313 - 323
Опубликована: Дек. 1, 2024
Язык: Английский
Процитировано
0