Explanipedia

PEGylation Enhances Colloidal Stability and Promotes Ligand-Mediated Targeting of LAF–Xenopeptide mRNA Complexes Open

Paul Folda, Eric Weidinger, Johanna Seidl, Mina Yazdi, Jana Pöhmerer , et al. · 2025

For complexation of mRNA into polyplexes, double-pH-responsive lipo-xenopeptides (XP), comprising tetraethylene pentamino succinic acid (Stp) and lipoamino fatty acids (LAFs), were combined with PEGylated lipids, either DMG-PEG 2 kDa (DMG-…

CRISPR/Cas9 Ribonucleoprotein Delivery Enhanced by Lipo-Xenopeptide Carriers and Homology-Directed Repair Modulators: Insights from Reporter Cell Lines Open

Xianjin Luo, Eric Weidinger, Tobias Burghardt, Miriam Höhn, Ernst Wagner · 2025

CRISPR-Cas9 genome editing is a versatile platform for studying and treating various diseases. Homology-directed repair (HDR) with DNA donor templates serves as the primary pathway for gene correction in therapeutic applications, but its e…

Dynamic Nanocarriers for RNA Delivery and Genome Editing Open

Ernst Wagner · 2025

Dual pH-responsive CRISPR/Cas9 ribonucleoprotein xenopeptide complexes for genome editing Open

Xianjin Luo, Janin Germer, Tobias Burghardt, Melina Grau, Yi Lin , et al. · 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), form…

New insights for the development of efficient DNA vaccines Open

Simone Berger, Yanira Zeyn, Ernst Wagner, Matthias Bros · 2024

Despite the great potential of DNA vaccines for a broad range of applications, ranging from prevention of infections, over treatment of autoimmune and allergic diseases to cancer immunotherapies, the implementation of such therapies for cl…

Unraveling the metastasis‐preventing effect of miR‐200c in vitro and in vivo Open

Bianca Köhler, E.M. BRIEGER, Tom Brandstätter, Elisa Hörterer, Ulrich Wilk , et al. · 2024

Advanced breast cancer, as well as ineffective treatments leading to surviving cancer cells, can result in the dissemination of these malignant cells from the primary tumor to distant organs. Recent research has shown that microRNA 200c (m…

Strategies and mechanisms for endosomal escape of therapeutic nucleic acids Open

Melina Grau, Ernst Wagner · 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 res…

Dual Effect by Chemical Electron Transfer Enhanced siRNA Lipid Nanoparticles: Reactive Oxygen Species-Triggered Tumor Cell Killing Aggravated by Nrf2 Gene Silencing Open

Fengrong Zhang, Tobias Burghardt, Miriam Höhn, Ernst Wagner · 2024

Insufficient endosomal escape presents a major hurdle for successful nucleic acid therapy. Here, for the first time, a chemical electron transfer (CET) system was integrated into small interfering RNA (siRNA) lipid nanoparticles (LNPs). Th…

Lipo-Xenopeptide Polyplexes for CRISPR/Cas9 based Gene editing at ultra-low dose Open

Janin Germer, Anna-Lina Lessl, Jana Pöhmerer, Melina Grau, Eric Weidinger , et al. · 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 a…

Tumor-targeted PROTAC prodrug nanoplatform enables precise protein degradation and combination cancer therapy Open

Zhifeng Zou, Lei Yang, Hui‐Jun Nie, Jing Gao, Shumin Lei , et al. · 2024

Dynamic carriers for therapeutic RNA delivery Open

Simone Berger, Ulrich Lächelt, Ernst Wagner · 2024

Carriers for RNA delivery must be dynamic, first stabilizing and protecting therapeutic RNA during delivery to the target tissue and across cellular membrane barriers and then releasing the cargo in bioactive form. The chemical space of ca…

Crosstalk Between NK Cell Receptors and Tumor Membrane Hsp70‐Derived Peptide: A Combined Computational and Experimental Study Open

Mina Yazdi, Morteza Hasanzadeh Kafshgari, Fatemeh Khademi Moghadam, Vahid Zarezade, Rupert Oellinger , et al. · 2024

Natural killer (NK) cells are central components of the innate immunity system against cancers. Since tumor cells have evolved a series of mechanisms to escape from NK cells, developing methods for increasing the NK cell antitumor activity…

Modulating efficacy and cytotoxicity of lipoamino fatty acid nucleic acid carriers using disulfide or hydrophobic spacers Open

Ricarda C. Steffens, Sophie Thalmayr, Eric Weidinger, Johanna Seidl, Paul Folda , et al. · 2024

Double pH-responsive xenopeptides comprising polar ionizable succinoyl tetraethylene pentamine (Stp) motifs and lipophilic ionizable lipoamino fatty acids (LAFs) were recently found to efficiently transfect mRNA and pDNA at low doses.

Transcriptional Targeting of Dendritic Cells Using an Optimized Human Fascin1 Gene Promoter Open

Yanira Zeyn, Dominika Hobernik, Ulrich Wilk, Jana Pöhmerer, Christoph Hieber , et al. · 2023

Deeper knowledge about the role of the tumor microenvironment (TME) in cancer development and progression has resulted in new strategies such as gene-based cancer immunotherapy. Whereas some approaches focus on the expression of tumoricida…

mCherry on Top: A Positive Read-Out Cellular Platform for Screening DMD Exon Skipping Xenopeptide–PMO Conjugates Open

Anna-Lina Lessl, Jana Pöhmerer, Yi Lin, Ulrich Wilk, Miriam Höhn , et al. · 2023

Phosphorodiamidate morpholino oligomers (PMOs) are a special type of antisense oligonucleotides (ASOs) that can be used as therapeutic modulators of pre-mRNA splicing. Application of nucleic-acid-based therapeutics generally requires suita…

From structural design to delivery: mRNA therapeutics for cancer immunotherapy Open

Feng Zhou, Lujia Huang, Shiqin Li, Wenfang Yang, Fangmin Chen , et al. · 2023

mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority in expressing all sequence‐known proteins in vivo. In particular, with a small dosage of delivered mRNA, antigen‐presenting cell…

Unravelling the metastasis-preventing effect of miR-200c in vitro and in vivo Open

Bianca Köhler, E.M. BRIEGER, Tom Brandstätter, Elisa Hörterer, Ulrich Wilk , et al. · 2023

Advanced breast cancer as well as insufficient treatment can lead to the dissemination of malignant cells from the primary tumor to distant organs. Recent research has shown that miR-200c can hamper certain steps of the invasion-metastasis…

Receptor-Targeted Carbon Nanodot Delivery through Polymer Caging and Click Chemistry-Supported LRP1 Ligand Attachment Open

Fengrong Zhang, Teoman Benli‐Hoppe, Wei Guo, Johanna Seidl, Yi Wang , et al. · 2023

Carbon nanodots present resistance to photobleaching, bright photoluminescence, and superior biocompatibility, making them highly promising for bioimaging applications. Herein, nanoprobes were caged with four-armed oligomers and subsequent…

Peptide nucleic acid-zirconium coordination nanoparticles Open

Özgür Öztürk, Anna-Lina Lessl, Miriam Höhn, Stefan Wuttke, Peter E. Nielsen , et al. · 2023

Ideal drug carriers feature a high loading capacity to minimize the exposure of patients with excessive, inactive carrier materials. The highest imaginable loading capacity could be achieved by nanocarriers, which are assembled from the th…

Interleukin-6-controlled, mesenchymal stem cell-based sodium/iodide symporter gene therapy improves survival of glioblastoma-bearing mice Open

Carolin Kitzberger, Khuram Shehzad, Volker Morath, Rebekka Spellerberg, Julius Ranke , et al. · 2023

New treatment strategies are urgently needed for glioblastoma (GBM)-a tumor resistant to standard-of-care treatment with a high risk of recurrence and extremely poor prognosis. Based on their intrinsic tumor tropism, adoptively applied mes…

High-resolution bioenergetics correlates the length of continuous protonatable diaminoethane motif of four-armed oligo(ethanamino)amide transfectants to cytotoxicity Open

Arnaldur Hall, Jiří Bártek, Ernst Wagner, Ulrich Lächelt, S. Moein Moghimi · 2023

Recent clinical success with Onpattro and cationic ionizable lipid nanoparticle-based mRNA vaccines has rejuvenated research in the design and engineering of broader synthetic cationic vectors for nucleic acid compaction and transfection. …

Chemical Evolution of Amphiphilic Xenopeptides for Potentiated Cas9 Ribonucleoprotein Delivery Open

Yi Lin, Xianjin Luo, Tobias Burghardt, Sarah Dorrer, Miriam Höhn , et al. · 2023

The introduction of the CRISPR/Cas9 system in the form of Cas9/sgRNA ribonucleoproteins (RNP) is an efficient, straightforward strategy for genome editing, and potent RNP carriers are in high demand. Here, we report a series of artificial …

Iron-Gallic Acid Peptide Nanoparticles as a Versatile Platform for Cellular Delivery with Synergistic ROS Enhancement Effect Open

Fa-Qian Shen, Yi Lin, Miriam Höhn, Xianjin Luo, Markus Döblinger , et al. · 2023

Cytosolic delivery of peptides is of great interest owing to their biological functions, which could be utilized for therapeutic applications. However, their susceptibility to enzymatic degradation and multiple cellular barriers generally …

Chemical-electron-transfer-based lipopolyplexes for enhanced siRNA delivery Open

Fengrong Zhang, Yi Lin, Miriam Höhn, Ernst Wagner · 2023

Endosomal escape remains a well-known bottleneck for successful small interfering RNA (siRNA) therapeutics. Here, a chemical electron transfer (CET)-based self-activatable lipopolyplex is explored for producing singlet oxygen (1O2) in endo…

Supplementary Figures 1 through 10 from V-ATPase Inhibition Regulates Anoikis Resistance and Metastasis of Cancer Cells Open