diff --git a/src/contents/engineering.tsx b/src/contents/engineering.tsx index 84b77760e4586a7a95e62eefabc28d0dad24e0eb..e46b55d7bf99529602a806040a2c57f2c445be11 100644 --- a/src/contents/engineering.tsx +++ b/src/contents/engineering.tsx @@ -567,7 +567,7 @@ export function Engineering() { <p id="del4"> <H3 text="Interation 4 - Spray-dried SORT LNP called Airbuddy" id="it4" /> The next design iteration incorporated the insights from Wang's LNP work for building upon SORT principles to make the nanoparticles lung-specific [6]. The main components include DMG-PEG 2000, cholesterol, DOPE and DOTAP as phospholipids and cationic lipids such as 4A3-SC8. In our LNP development, we carefully considered the use of PEG. While PEG can improve stability, it can also reduce cellular uptake and induce immune responses, necessitating a balanced approach to its inclusion [7]. - <Collapsible id="Col1" open={false} title="Ambivalence of PEG and our implementation"> + <Collapsible id="Col1" open={false} title="Ambivalence of PEG and our implementation // LNP Handbook Cooperation"> <p> <H4 text="What is PEG and why is it important for LNPs?" id="text" /> Polyethylene glycol (PEG) is an essential component in the formulation of lipid nanoparticles (LNPs), which are widely used in drug delivery systems, particularly for mRNA-based therapies like vaccines. PEG-lipids are hybrid molecules consisting of a hydrophilic PEG chain attached to a hydrophobic lipid anchor. This unique structure enables PEG-lipids to interact effectively with both aqueous environments and lipid structures, such as cell membranes and lipid nanoparticles themselves. @@ -587,7 +587,7 @@ export function Engineering() { We use DMG-PEG2000 in our SORT LNP-based AirBuddy because of its superior biodegradability, enhanced stability, and reduced risk of immune system activation. By building on insights from experts and incorporating principles from Wang’s LNP work, we’ve tailored our nanoparticles for lung-specific delivery. This choice ensures that our formulations remain stable long enough to deliver the therapeutic payload effectively while minimizing potential long-term toxicity. This balance is crucial for pulmonary applications, where DMG-PEG2000 outperforms alternatives like mPEG-2000-DSPE, making it the ideal choice for treating CFTR-related lung diseases. </p> </Collapsible> - <p>DMG-PEG2000 of the SORT LNP offers better biodegradability and enhanced stability in pulmonary applications - it is known for its faster clearance and reduced potential for long-term toxicity. To ensure we addressed this issue, cytotoxicity tests were performed in addition to the determination of physical properties in cooperation with the Physical and Biophysical Chemistry working group of Bielefeld University to characterize the LNPs. More details about the composition of the SORT LNPs and function of the components can be read below.</p> + <p>DMG-PEG2000 of the SORT LNP offers better biodegradability and enhanced stability in pulmonary applications - it is known for its faster clearance and reduced potential for long-term toxicity. To ensure we addressed this issue, cytotoxicity tests were performed in addition to the determination of physical properties in cooperation with the <a onClick={() => goToPagesAndOpenTab('biophysik', '/human-practices')}>Physical and Biophysical Chemistry working group of Bielefeld University</a> to characterize the LNPs. More details about the composition of the SORT LNPs and function of the components can be read below.</p> <figure> <img src="https://static.igem.wiki/teams/5247/delivery/sort-lnp-freigestellt.webp" alt="AirBuudy"/> <figcaption> @@ -618,7 +618,7 @@ export function Engineering() { <figure> <img src="https://static.igem.wiki/teams/5247/delivery/big-plan-inhalation-teil-del.webp" alt="Flow DEL"/> <figcaption> - <b>Figure. </b> + <b>Figure 4. </b> Application stategy - AirBuddy is inhaled by the patient, enabling uptake of PrimeGuide in lung epithelial cells via endocytosis. </figcaption> </figure> @@ -628,7 +628,7 @@ export function Engineering() { <div className="box" > <p id="del5"> <H3 text="Outlook" id="text" /> - Ultimately, through continuous cycles of experimentation, feedback, and optimization, a LNP formulation called AirBuddy was designed using SORT LNPs and a spray-drying process, achieving lung specificity and improved safety. We also want to state that for our LNP is further room for improvement. Intensive research led us to the realization that, among other modifications, <strong>antibody conjugation</strong> as a surface modification of our LNP for cell type-specific administration, more specifically club cells [9] and ionocytes [11] as most CFTR-expressing lung epithelial cells, would round off our most important aspect of precision. In addition, the discussion with Benjamin Moorlach, chitosan expert working at FH Bielefeld, provided new ideas for improvement by <strong>complexing the mRNA with chitosan</strong> to improve the stability of the cargo during spray drying and nebulization. + Ultimately, through continuous cycles of experimentation, feedback, and optimization, a LNP formulation called AirBuddy was designed using SORT LNPs and a spray-drying process, achieving lung specificity and improved safety. We also want to state that for our LNP is further room for improvement. Intensive research led us to the realization that, among other modifications, <strong>antibody conjugation</strong> as a surface modification of our LNP for cell type-specific administration, more specifically club cells [9] and ionocytes [11] as most CFTR-expressing lung epithelial cells, would round off our most important aspect of precision. In addition, the discussion with <a onClick={() => goToPagesAndOpenTab('moorlach', '/human-practices')}>Benjamin Moorlach</a>, chitosan expert working at FH Bielefeld, provided new ideas for improvement by <strong>complexing the mRNA with chitosan</strong> to improve the stability of the cargo during spray drying and nebulization. </p> </div> <br/>