gene therapy - CarboHyde

Oligonucleotide Formulations Prepared by High-Speed Electrospinning: Maximizing Loading and Exploring Downstream Processability

Mar 20, 2023Tamas Sohajdadrug deliverygene therapy

today’s cyclodextrin:
is about developing antisense oligonucleotide tablet formulations using high-speed electrospinning. Hydroxypropyl-beta-cyclodextrin (HPβCD) was used as a stabilizer and an electrospinning matrix from one of the best pharma groups in Hungary (FirePharma Research Group BME – Budapest University of Technology and Economics) collaborating with Janssen Inc.

The fibrous HPβCD–antisense oligonucleotide formulations showed no sign of physical or chemical degradation over the 1-year stability study, which also shows the suitability of the HPβCD matrix for the formulation of biopharmaceuticals. The obtained results demonstrate possible solutions for the challenges of electrospinning, such as scale-up and downstream processing of the fibers.

Edit Hirsch, Márió Nacsa, Edina Szabó, Panna Vass, Julia Domjan, Attila Farkas,Zsuzsanna Eke, Tamás Vigh, Sune Klint Andersen, Geert Verreck, György Marosi and Zsombor Kristof Nagy et al

See the full article here: Oligonucleotide Formulations Prepared by High-Speed Electrospinning: Maximizing Loading and Exploring Downstream Processability

Chemistry, structure and function of approved oligonucleotide therapeutics

Mar 16, 2023Tamas Sohajdacarbohydratesgene therapy

Chemistry, structure and function of approved #oligonucleotide therapeutics by Martin Egli (Vanderbilt University) and Muthiah (Mano) Manoharan (Alnylam Pharmaceuticals).
Eighteen nucleic acid therapeutics have been approved for the treatment of various diseases in the last 25 years. Their modes of action include antisense oligonucleotides (ASOs), splice-switching oligonucleotides (SSOs), RNA interference (RNAi) and an RNA aptamer against a protein.
Oligonucleotide therapeutics brought to market thus far contain just a handful of first- and second-generation modifications, among them 2′-fluoro-RNA, 2′-O-methyl RNA, and the phosphorothioates that were introduced over 50 years ago. Two other privileged chemistries are 2′-O-(2-methoxyethyl)-RNA (MOE) and the phosphorodiamidate morpholinos (PMO). Given their importance in imparting oligonucleotides with high target affinity, metabolic stability, and favorable pharmacokinetic and -dynamic properties, this article provides a review of these chemistries and their use in nucleic acid therapeutics. Breakthroughs in lipid formulation and GalNAc conjugation of modified oligonucleotides have paved the way to efficient delivery and robust, long-lasting silencing of genes. This review provides an account of the state-of-the-art of targeted oligo delivery to hepatocytes.

See the full article here: Chemistry, structure and function of approved oligonucleotide therapeutics

Controlled drug delivery mediated by cyclodextrin-based supramolecular self-assembled carriers: From design to clinical performances

Mar 10, 2023Tamas SohajdaToday's cyclodextrinformulation development, gene therapy

today’s #cyclodextrin:
achieving controlled release with cyclodextrins can be really challenging, yet it is doable. In fact, there are multiple strategies to get there. In this review, Jana Ghitman and Voicu Stefan Ioan collected different approaches of cyclodextrins-based drug delivery forms that are suitable for co-delivery systems, non-viral vectors for gene delivery, and theranostics.
This review presents the latest achievements in nanoparticle-based supramolecular architectures, taking into account the main synthesis methods and the stimuli that control the release (light-responsive, pH-responsive, redox-responsive, and multi-responsive). The review also presents applications and also the present status regarding commercial systems based on cyclodextrins and their characteristics.

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Controlled drug delivery mediated by cyclodextrin-based supramolecular self-assembled carriers: From design to clinical performances

Cyclodextrin-Based Nanoparticles for Delivery of Antisense Oligonucleotides Targeting Huntingtin

Feb 9, 2023Tamas Sohajdadrug deliverygene therapy, genegut, Huntington disease

Check out the most recent paper of our collaborators in the GENEGUT Horizon Europe consortia presenting cyclodextrin-based nanoparticles for delivery of antisense oligonucleotides targeting huntingtin. Even if we were not part of this story, we are proud to get involved in the next chapter!

University College Cork – Monique Culturato Padilha Mendonça, PhD, Caitriona O’Driscoll et al
APC Microbiome Ireland – John Cryan

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Passive, active and endogenous organ-targeted lipid and polymer nanoparticles for delivery of genetic drugs

Jan 23, 2023Tamas Sohajdadrug deliverygene therapy, lipid, polymer

As fellow stakeholders in developing novel drug delivery in gene therapy, we greatly admire the review of Sean Dilliard and Daniel Siegwart from The University of Texas Southwestern Medical School describing passive, active and endogenous organ-targeted lipid and polymer nanoparticles. Amazing compilation!

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Two papers on the uses of hyper-branched CD-polymer:

Dec 8, 2022Tamas SohajdaToday's cyclodextrincalcium, coagulation, dna, drug delivery, drug development, gene therapy

Fresh from the oven of the Francesco Trotta and Adrián Matencio Durán (Università degli Studi di Torino) lab, two papers on the uses of hyper-branched CD-polymer:
No 1: use as an anticoagulant, which is a very innovative application for CDs that are getting more and more spotlight

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No 2: use as transfection promoters of plasmids.

See the full article here.

I congratulate you on this ambitious research goal, loved both papers and look forward to seeing from sprouting from the collaboration you recently started with CarboHyde!
Yousef Khazaei monfared, Mohammad Mahmoudian, Claudio Cecone, Fabrizio Caldera, Sanya Haiaty, Reza Rahbarghazi, Parvin Zakeri-Milani, Gjylije Hoti, Fabrizio Caldera, Roberta Cavalli