Diagnostic and Therapeutic Advances of RNAs in Precision Medicine of Gastrointestinal Tumors DOI Creative Commons
Runhan Liu, Jiaxin Zhou, Xiaochen Chen

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 13(1), P. 47 - 47

Published: Dec. 28, 2024

Gastrointestinal tumors present a significant challenge for precision medicine due to their complexity, necessitating the development of more specific diagnostic tools and therapeutic agents. Recent advances have positioned coding non-coding RNAs as emerging biomarkers these malignancies, detectable by liquid biopsies, innovative Many RNA-based therapeutics, such small interfering RNA (siRNA) antisense oligonucleotides (ASO), entered clinical trials or are available on market. This review provides narrative examination potential in gastrointestinal cancers, with an emphasis its application medicine. discusses current challenges, drug resistance tumor metastasis, highlights how molecules can be leveraged targeted detection treatment. Additionally, this categorizes targets based tissue type, offering comprehensive analysis role advancing tumors.

Language: Английский

Lipo-Xenopeptide Polyplexes for CRISPR/Cas9 based Gene editing at ultra-low dose DOI Creative Commons

Janin Germer,

Anna-Lina Lessl,

Jana Pöhmerer

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 370, P. 239 - 255

Published: April 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

Language: Английский

Citations

3
Dual pH-responsive CRISPR/Cas9 ribonucleoprotein xenopeptide complexes for genome editing DOI Creative Commons

Xianjin Luo,

Janin Germer,

Tobias Burghardt

et al.

European Journal of Pharmaceutical Sciences, Journal Year: 2024, Volume and Issue: 205, P. 106983 - 106983

Published: Dec. 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.

Language: Английский

Citations

2
Amphiphilic Dynamic Covalent Polymer Vectors of siRNA DOI Creative Commons
José García Coll,

Pauline Trousselier,

Sachin Dattram Pawar

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 30, 2024

Hydrophobization of peptide-based dynamic covalent polymer vectors boosts their siRNA delivery performances.

Language: Английский

Citations

2
Special delivery DOI

Philip Ball

Nature Materials, Journal Year: 2024, Volume and Issue: 23(4), P. 442 - 442

Published: April 1, 2024

Citations

1
Dual conjugation of magnetic nanoparticles with antibodies and siRNA for cell-specific gene silencing in vascular cells DOI Creative Commons
Katarzyna Karpińska-Kaczmarczyk, Lin Li, Tao Wang

et al.

Frontiers in Drug Delivery, Journal Year: 2024, Volume and Issue: 4

Published: Aug. 15, 2024

RNA therapy is a rapidly expanding field and has great promise in achieving targeted gene silencing contributing to personalized medicine. However, the delivery of molecules into organs or cells still challenging. To overcome this hurdle, number nanocarriers with pros cons have been developed. This study was designed develop simple cost-effective approach functionalize biodegradable magnetic iron nanoparticles (MNPs) for cell-specific siRNA delivery. MNPs were synthesized based on co-precipitation further functionalized sodium citrate polyethyleneimine (PEI) followed by material characterization using TEM, FTIR, Zeta potential. The PEI-coated conjugated CD31 antibody complexed linker-free approach. siRNA-loaded successfully knocked down expression GAPDH human endothelial (ECs) NOTCH3 vascular smooth muscle (VSMCs). In an EC VSMC co-culture system under shear stress mimic blood flow, specifically delivered ECs. Our represents versatile platform that could be adopted general

Language: Английский

Citations

1
Quinine-Based Polymers Are Versatile and Effective Vehicles for Intracellular pDNA, mRNA, and Cas9 Protein Delivery DOI
Punarbasu Roy, Nicholas W. Kreofsky, Theresa M. Reineke

et al.

Biomacromolecules, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

Quinine-based polymers have previously demonstrated promising performance in delivering pDNA cells owing to their electrostatic as well the nonelectrostatic interactions with pDNA. Herein, we evaluate whether quinine-based are versatile for delivery of mRNA and Cas9-sgRNA complexes, especially a serum-rich environment. Both complex potent therapeutics that structurally, chemically, functionally very different from By exploring family 7 vary monomer structure polymer composition, tested numerous formulations (42 pDNA, 96 mRNA, 48 Cas9-sgRNA) payload-polymer complexation compare payload-dependent structure-activity relationships. Several comparable or better than commercially available transfection agent jetPEI. The results this study demonstrate potential carrier platform wide range nucleic acid serving drug needs field genetic medicine.

Language: Английский

Citations

1
Modulating efficacy and cytotoxicity of lipoamino fatty acid nucleic acid carriers using disulfide or hydrophobic spacers DOI Creative Commons

Ricarda C. Steffens,

Sophie Thalmayr,

Eric Weidinger

et al.

Nanoscale, Journal Year: 2024, Volume and Issue: 16(29), P. 13988 - 14005

Published: Jan. 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.

Language: Английский

Citations

0
Biomimetic Nucleic Acid Drug Delivery Systems for Relieving Tumor Immunosuppressive Microenvironment DOI Creative Commons

Wenlu Yan,

Ying Cao, Qi Yin

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(8), P. 1028 - 1028

Published: Aug. 1, 2024

Immunotherapy combats tumors by enhancing the body's immune surveillance and clearance of tumor cells. Various nucleic acid drugs can be used in immunotherapy, such as DNA expressing cytokines, mRNA vaccines, small interfering RNAs (siRNA) knocking down immunosuppressive molecules, oligonucleotides that adjuvants. Nucleic drugs, which are prone to nuclease degradation circulation find it difficult enter target cells, typically necessitate developing appropriate vectors for effective vivo delivery. Biomimetic drug delivery systems, derived from viruses, bacteria, protect cargos clearance, deliver them cells ensure safety. Moreover, they activate system through their endogenous activities active components, thereby improving efficacy antitumor immunotherapeutic drugs. In this review, biomimetic systems relieving a microenvironment introduced. Their activation mechanisms, including upregulating proinflammatory serving inhibiting checkpoints, modulating intratumoral elaborated. The advantages disadvantages, well possible directions clinical translation, summarized at last.

Language: Английский

Citations

0
Icariin-Enhanced Osteoclast-Derived Exosomes Promote Repair of Infected Bone Defects by Regulating Osteoclast and Osteoblast Communication DOI Creative Commons
Yang Zhang, Minjie Zhang, Mengying Li

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 12389 - 12407

Published: Nov. 1, 2024

Infected bone defects pose a challenging clinical issue due to an imbalance of osteoclasts (OC) and osteoblasts (OB). Exosomes are crucial for intercellular signaling OC OB in repair. Icariin, has been shown regulate the balance between OB. However, specific mechanisms by which icariin influences exosomes derived from osteoclasts, subsequently impacts osteoblast activity, remain unclear. This study aims investigate effects icariin-treated osteoclast-derived (ICA-OC-Exo) on function repair cases infected defects.

Language: Английский

Citations

0
Chitosan nanoparticles in tissue engineering and regenerative medicine DOI

Farzaneh Jabbari,

Marzieh Ramezani Farani,

Atiye Abednejad

et al.

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 497 - 526

Published: Nov. 29, 2024

Language: Английский

Citations

0