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.
Today’s cyclodextrin is some gene delivery again, as it is also a focus project at CarboHyde.
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.
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. 🌟
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!
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 💡
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.
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.
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.
Another great application using cyclodextrin in non-viral drug delivery for gene therapy is presented in this paper underlining the versatility of these compounds in this field – similar in application to what we are working on in GENEGUT. Colleagues present a novel targeting bio-conjugate for selective delivery of therapeutic nucleic acids, including RNA oligonucleotides and DNA- oligonucleotides, preferably gene-encoding DNA plasmids or minicircle DNAs, to eukaryotic cells by means of receptor-mediated endocytosis and endosomal release. Dietmar Appelhans et al.
