aimofcontact:[<p>The aim of the interview was to gain expert insights on optimizing the delivery of CFTR-mRNA via lung-targeted lipid nanoparticles (LNPs) for cystic fibrosis (CF) treatment.
Specifically, the goal was to explore potential cell targets, challenges in delivery mechanisms, and technical tools for assessing the effectiveness of mRNA therapies like the Ussing chamber system. </p>],
insights:[<p>The experts highlighted the potential of targeting ionocytes, given their key role in CFTR expression, but emphasized the difficulty in accessing them due to their basal position in the respiratory epithelium.
quote:"We hadn’t initially considered patch-clamp measurements in our set of downstream applications, but it’s proven to be an exceptionally sensitive method for assessing CFTR conductance.",
quote:"Initially we hadn't considered patch-clamp measurements in our set of downstream applications, but it’s proven to be an exceptionally sensitive method for assessing CFTR conductance.",
aimofcontact:[<p>As part of our project, we aimed to demonstrate the functionality of the CFTR ion channel, after restoring
it through our optimized Prime Editing, by using Patch-Clamp measurements. To ensure the optimal use of the
Patch-Clamp and to gain an insight into electrophysiology, we asked experts from the medical faculty at
heading:"Lipid Nanoparticles in Gene Therapy: perspectives from Corden Pharma ",
interviewtabid:"corden",
cardtext:"",
language:"de",
quote:"",
aimofcontact:"",
insights:"",
implementation:"",
},
aimofcontact:[<p>The goal of the discussion with Steffen Bira and Serra Gürcan from Corden Pharma was to gain insight into the design, stability, and practical application of lipid nanoparticles (LNPs) for use in gene therapy.
The conversation focused on the possibility of using Corden Pharma’s LNP starter kits, understanding the factors affecting the stability of LNPs, and exploring options for incorporating antibodies into LNPs to target specific cells. </p>],
insights:[<p>Steffen Bira and Serra Gürcan of Corden Pharma indicated that our planned spray drying approach of LNPs has not been extensively explored within their operations. The company focuses primarily on the aseptic fill and finish of LNPs, particularly for injectable formulations.
However, they acknowledged the potential for spray drying and recommended consulting with specialized companies to assess the feasibility. The stability of the lipids used in LNPs during the spray drying process was also identified as an area requiring further investigation.
The stability of LNPs, in particular in the context of the shear forces encountered in inhalation therapy, was identified as a critical factor. Corden Pharma highlighted that while the stability of individual lipid components can be evaluated, the stability of a complete LNP
formulation containing RNA or other payloads must be empirically tested. The company put forward the suggestion that cryoprotectants and varying temperature conditions might be considered to enhance the stability of LNPs during processing. Corden Pharma outlined the process
used to select the lipids included in their LNP starter kits, nothing that these combinations are based on established interactions and research findings, particularly in RNA-containing formulations. The kits are designed to facilitate the creation of stable LNPs by providing
materials that have been tested for their physical-chemical properties, encapsulation efficiency, and potency. Furthermore, the company highlighted that a single LNP starter kit can be used for multiple batches, offering a practical solution for experimental work.
When asked about modifying lipid components within LNP formulations, Corden Pharma suggested that exploring alternative lipids and other components could be beneficial for improving stability and efficacy, depending on the specific needs of the project.
We discussed the availability of various lipids, including derivatives of cholesterol, which might enhance transfection efficiency in certain cell types. Corden Pharma confirmed that it is also possible to incorporate antibodies into LNPs, either during the initial preparation phase or by incubating
antibodies with formed LNPs to achieve surface localization. While they did not have hands-on experience in this specific application, they referenced existing studies that could provide further guidance.
Corden Pharma clarified that their role as a Contract Development and Manufacturing Organization (CDMO) is focused on providing services for the production of active pharmaceutical ingredients (APIs) and excipients, rather than developing therapeutic products. They advised that intellectual property (IP)
considerations are crucial when selecting lipids for LNP formulations, especially in commercial applications, as many lipids are patented. Companies pursuing gene therapy projects should ensure that the lipids they choose are free from IP restrictions or be prepared to pay associated fees.
The possibility of establishing a collaborative relationship was discussed, with Corden Pharma open to the idea of offering discounts on LNP starter kits or other materials in exchange for recognition in publications or other forms of acknowledgment. This proposal is subject to internal approval and would be pursued further through direct communication. </p>],
implementation:[<p>The cooperation with Cordon Pharma provided invaluable insights for the project, particularly regarding the selection of lipids critical LNP stability and the potential applications of LNPs in gene therapy. Our initial approach involved utilising the Cayman kit, which proved to be suboptimal for the intended delivery of our Primeguide.
The Corden Pharma kit #2 offers enhanced delivery efficiency thanks to its cutting-edge lipid components, including cationic lipids that boost cellular uptake and auxiliary lipids that reinforce the LNP structure. However, we have subsequently updated our approach and now use the Corden Pharma Kit, which builds on these benefits by including even more optimised lipid formulations. This change allows us to further improve the robustness and stability of our LNP formulations. The insights gained from the survey will significantly influence our testing process and enable us to optimise the delivery of therapeutic agents and improve overall treatment efficacy. </p>],
interview:<>
<QaBoxq="Is it possible to dry the LNPs designed by Corden Pharma, like through spray drying?"a="It’s not confirmed yet if LNPs can be successfully dried using spray drying. It would need some further research or a chat with a specialized company to figure that out."/>
<QaBoxq="How is stability ensured in LNPs, especially for inhalation therapy?"a="The stability of LNPs mostly depends on the specific lipid and RNA components in the mix. While we can check how stable individual lipids are, we really need to do some hands-on testing to see how stable a new LNP formulation is under different conditions."/>
<QaBoxq="How are lipid combinations chosen for the LNP starter kits, and what testing happens?"a="The lipid combos in the LNP starter kits are picked based on known interactions, especially for RNA formulations. Testing includes checking the physical-chemical properties, how well things are encapsulated, and overall effectiveness. The kits come with enough material for multiple experimental batches."/>
<QaBoxq="Should we modify the lipid components in an existing LNP formulation?"a="It’s usually a good idea to think about alternative lipid components since different ones might offer better stability or effectiveness. But whether to make changes really depends on what your project needs."/>
<QaBoxq="Can we add antibodies into LNPs, and how do we do that?"a="Yes, you can definitely incorporate antibodies into LNPs! You can do this either during the initial prep phase or by mixing them in after the LNPs are formed, depending on whether you want the antibodies on the surface or inside. Checking out specific studies might help with this."/>
<QaBoxq="What’s Corden Pharma’s take on gene therapy projects?"a="Corden Pharma is mainly a service provider, focusing on making active pharmaceutical ingredients (APIs) and excipients rather than developing therapeutic products. Just keep in mind the intellectual property status of the lipids used in LNP formulations, especially for commercial use."/>
<QaBoxq="Can we get a discount on LNP starter kits or partner with Corden Pharma?"a="We’ll need to chat about this internally, but generally, we’re open to the idea. There’s a chance we could get a discount or set up a collaboration, especially if it leads to recognition in publications or other forms of acknowledgment—pending approval from the right people, of course."/>
