If it’s gene delivery and custom cyclodextrins – count us in!

Jun 19, 2026admindrug discoverycyclodextrin, gene therapy

In this study – differing from the GENEGUT concept – our CSO, Milo Malanga PhD, designed cyclodextrin polymers that can form nanoplexes with various oligonucleotides due to their cationic nature. The we compared them with a standard polymer in the field: polyethylenimine.

QABCDPS exhibited lower toxicity compared to PEI, effectively binding both siRNA and mRNA and delivering them into vesicles in the cytoplasm, but showing different internalization patterns.

Polyplexes formed with PEI showed stronger biological effect than those with QABCDPS, which can be attributed to the strength of interactions facilitated by the polymers.

We hope to continue the collaboration with University of Debrecen – especially Ágnes Rusznyák and Ferenc Fenyvesi and design more efficient shuttles for the next round.

Comparison of the siRNA and mRNA Carrying Capacity of Quaternary Ammonium β-Cyclodextrin Polymer and Polyethylenimine

pharmaceutics-18-00713 Download

Cationic Cyclodextrin-Based Carriers for Drug and Nucleic Acid Delivery

Jan 10, 2025Tamas SohajdaToday's cyclodextrin, drug deliverygene therapy

Check out our latest cyclodextrin review fresh from the oven on cationic cyclodextrins for drug and nucleic acid delivery.

This contribution to science is a fruit of our collaboration with Eötvös Loránd University and Semmelweis University (Szabolcs Béni and Adila Nazli).

Special thanks to Milo Malanga PhD and Tamas Sohajda as well as Bicyclos HEurope for the funding.

Cationic Cyclodextrin-Based Carriers for Drug and Nucleic Acid Delivery

Cationic Cyclodextrin-Based Carriers for Drug and Nucleic Acid Delivery

Structure-activity relationship of modified amphiphilic cationic cyclodextrins for enhanced siRNA delivery

Jan 6, 2025Tamas SohajdaEgyéb kategória, Today's cyclodextrincyclodextrin, gene therapy, genegut

Today’s cyclodextrin was a little gift under CarboHyde’s and GENEGUT’s Christmas tree.

This study identified the structural modifications that enhance gene delivery activity of a range of cationic amphiphilic CDs, including both β- and γ-CD.

Each CDs incorporated a C12 lipid chain on the primary face of the CD. On the secondary rim, at positions C2 and C3, either primary or tertiary amine groups.

A comparative in vitro study was conducted to assess the gene silencing efficacy of these nanoparticles using the luciferase reporter gene in A549-luc cells.

Gene silencing levels for both β- and γ-CDs increased when modified with a primary amine compared to a tertiary amine group at position C2. Gene expression inhibition was further improved when the CDs were functionalized with amine functionalities at positions C2 and C3.

Modification of the secondary side of γ-cyclodextrins with two sets of primary amine functionalities via a thiopropyl linker, as compared to a triazole linker, achieved up to 80% gene knockdown, regardless of dose.

Ayse Kont, Monique Mendonça, PhD, Milo Malanga PhD, Kristóf Felegyi, Andrew Lindsay, Michael Cronin, Mary Cahill, Caitriona O’Driscoll

Structure-activity relationship of modified amphiphilic cationic cyclodextrins for enhanced siRNA delivery – ScienceDirect

Active transfection of genetic materials using cyclodextrin-anchored nanovectors

Dec 5, 2024Tamas SohajdaToday's cyclodextrincyclodextrin, gene therapy

Today’s cyclodextrin is some gene delivery again, as it is also a focus project at CarboHyde.

Gene-based therapy is a sophisticated means for the treatment of various complex diseases like AIDS, cancer, etc., as it resolves the genetic malfunction at the source instead of tackling the superficial symptoms. However, the therapeutic, diagnostic, and theranostic potential of gene-based therapeutic actives such as siRNA, mRNA, pDNA, aptamers, etc. is hindered by physicochemical as well as physiological barriers in the form of insufficient bioavailability, systemic metabolism, rapid renal clearance, inefficient carrier systems, etc.

This review article by Amey Revdekar, Bhagyashree Salvia and Pravin Shende features cyclodextrins and associated successful applications as the integral components of non-viral nanovectors such as cationic polymers, dendrimers and polyrotaxanes as well as supramolecular assemblies for efficient delivery of RNA-, DNA- and aptamer-based genetic payloads for the achievement of desired treatment outcomes.

Active transfection of genetic materials using cyclodextrin-anchored nanovectors – Materials Advances (RSC Publishing)

How do you see the future of cell and gene therapy?

Jul 2, 2024Tamas Sohajdadrug developmentbiologics, cell therapy, CPHI, gene therapy

Our concise outlook is the following:

Transformational Potential: Cell and gene therapies are revolutionizing how we treat diseases, promising to cure certain conditions.
They remain at the forefront of healthcare innovation.

Fast-Growing Field: These therapies are the fastest-growing therapeutics areas, with over 50 new in vivo and ex vivo gene therapy launches planned in the next few years.

Challenges and Innovation: While promising, cell and gene therapies require substantial innovation to unlock their full potential for patients. Scaling digital and analytics in discovery and R&D is part of the solution.

Market Resilience: Despite the disruptions caused by the pandemic, stakeholders, including CGT innovators, healthcare providers, and CDMOs, are optimistic that positive developments lie ahead.

Viral-Vector Therapies: Viral-vector gene therapies are here to stay, but addressing challenges and strategizing for patient access is critical for their success.

Overall, the outlook is positive, but ongoing research, regulatory advancements, and manufacturing innovations will shape the future of cell and gene therapy. 🌟

Lipid nanoparticles for nucleic acid delivery

Jul 1, 2024Tamas Sohajdadrug delivery, Today's cyclodextringene therapy, nucleic acid, oligonucleotides

Today’s cyclodextrin is this great patent from Roquette‘s team, Tao Peng, Lucas Goh, Jeff Chang Shih Chieh on a new class of Lipid nanoparticles (LNPs) that can be used for nucleic acid delivery, wherein LNPs comprise a nucleic acid and a nonionic or cationic cyclodextrin compound.

How do you see the future of CDs in gene therapy? Will we see solutions commercialized in the future? In GENEGUT we certainly work towards this goal!

WO2024125823 LIPID NANOPARTICLES FOR NUCLEIC ACID DELIVERY (wipo.int)

GENEGUT meeting in Porto

Jun 19, 2024adminnews, Today's cyclodextrinCrohn disease, gene therapy, HorizonEUrope, nanotherapeutics

Today’s #yclodextrin is about the fantastic progression of the GENEGUT project CarboHyde is part of.

The 5th in-person General Assembly meeting was kindly hosted by our partners at i3S – Instituto de Investigação e Inovação em Saúde, Bruno Sarmento, Catarina Leite Pereira in Porto, PT 🚀

We (Kristóf Felegyi) reported the chemistry work, which was our part, and now look forward to seeing how these building blocks will perform in RNA delivery and eventually in drug formulation. Caitriona O’Driscoll and Ana Francisca Soares presented some of the promising data at the 21st International Cyclodextrin Symposium last week.

We look forward to interesting discussions, progress updates and networking within the GENEGUT consortium 💡

Synthesis and Preliminary Evaluation of an ASGPr-Targeted Polycationic β-Cyclodextrin Carrier for Nucleosides and Nucleotides

Mar 8, 2024Tamas Sohajdadrug deliveryantiviral, cyclodextrin, gene therapy, polymer

As our interest to use cyclodextrin in genetherapy as superior drugdelivery tools continue, we welcome papers like this, where cationic CD polymers are used for nucleotide formulation.
Leonard Wiebe and coworkers from University of Alberta development a carrier designed to effect selective transmembrane internalization of nucleotides via the asialoglycoprotein receptor.

Pharmaceutics | Free Full-Text | Synthesis and Preliminary Evaluation of an ASGPr-Targeted Polycationic β-Cyclodextrin Carrier for Nucleosides and Nucleotides (mdpi.com)

Where do you expect its greatest impact in the future?

Jan 24, 2024Tamas Sohajdadrug discoverygene editing, gene therapy

For more than a decade, the CRISPR toolbox and its applications have profoundly changed biological research, enabling advances through applications in plants, animals, and humans.

Sustained Delivery of Cu(II)-Based DNA Intercalators by Nanometer-Sized Cyclodextrin-Based Porous Polymers

Nov 29, 2023Tamas Sohajdadrug discoverycyclodextrin, gene therapy, nanoparticle, polymer

Apparently, cyclodextrin-based oligonucleotide delivery is becoming a hot research topic. This recent study from University of Nova Gorica – Tina Škorjanc, PhD, Damjan Makuc, Nora Kulak, and Valant Matjaz presents a cyclodextrin porous polymer to form nanometer-sized particles and used as a delivery vehicle for metal-free and Cu(II)-metalated anthraquinone-based DNA intercalators.

Sustained Delivery of Cu(II)-Based DNA Intercalators by Nanometer-Sized Cyclodextrin-Based Porous Polymers | ACS Applied Nano Materials