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

drug development, , ,

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

drug delivery, Today's cyclodextrin, ,

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

news, Today's cyclodextrin, , ,

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 💡

GENEGUT, Porto, Horizon EUrope

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

drug delivery, , ,

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)


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

drug discovery, , ,

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

Targeted delivery of oligonucleotides into eukaryotic cells using hybrid maltose/cyclodextrin polyplexes

drug delivery

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.

WO2023169899 TARGETED DELIVERY OF OLIGONUCLEOTIDES INTO EUKARYOTIC CELLS USING HYBRID MALTOSE/CYCLODEXTRIN POLYPLEXES (wipo.int)

Glycosylation shapes the efficacy and safety of diverse protein, gene and cell therapies

carbohydrates, ,

Glycosylation, a near-universal feature of this class of drugs, is a critical quality attribute that significantly influences the physical properties, safety profile and biological activity of therapeutic proteins. Optimizing protein glycosylation offers an important avenue to developing more efficacious therapies.
In this review, Nathan Lewis’s team discusses specific examples of how variations in glycan structure and glycoengineering impact the stability, safety, and clinical efficacy of protein-based drugs that are already in the market and those still in preclinical development. We also highlight the impact of glycosylation on next-generation biologics such as T cell-based cancer therapy and gene therapy.

Please see the full article in this link!

Lipid-based RNA formulations suitable for therapy

Today's cyclodextrin, , , ,

today’s cyclodextrin:
In this invention, BioNTech SE provides a method of producing a composition comprising RNA lipoplex particles. The main focus of the description is antitumoral therapy.
In the formulation itself, the aqueous colloidal suspension of liposomes is combined with an aqueous solution comprising RNA, thereby producing the composition comprising RNA lipoplex particles. The formulation requires frozen storage conditions; hence the use of cyroprotectant is necessary. The invention proposes mono- di- and oligosaccharides to protect such compositions, including various cyclodextrins and cyclodextrin polymers.
The use of cyclodextrins as cryoprotectants and stabilizers in biopharmaceutical formulations is an emerging technology.

Dr. Hossam Hefesha, Heinrich Haas, Ferdia Bates, Christian Hotz
Katalin Karikó

See the full patent Patentscope

Influence of Sugar Modifications on the Nucleoside Conformation and Oligonucleotide Stability: A Critical Review

carbohydrates, ,

Ribofuranose sugar conformation plays an important role in the structure and dynamics of functional nucleic acids such as siRNAs, AONs, aptamers, miRNAs, etc. Several chemical modifications have been introduced into sugar moiety to improve their therapeutic potential over the years. The stability of the oligonucleotide duplexes as well as the formation of stable and functional protein-oligonucleotide complexes are dictated by the conformation and dynamics of the sugar moiety. In this review, Gourav Das Harikrishna and Kiran Gore systematically categorize various ribofuranose sugar modifications employed in DNAs and RNAs so far. We discuss different stereoelectronic effects imparted by different substituents on the sugar ring and how these effects control sugar puckering. Using this data, it would be possible to predict the precise use of chemical modifications and design novel sugar-modified nucleosides for therapeutic oligonucleotides that can improve their physicochemical properties.

See the full article here: Influence of Sugar Modifications on the Nucleoside Conformation and Oligonucleotide Stability: A Critical Review