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Unlock your research potential with Helix Biotech! ?? We are leading the charge in custom mRNA synthesis and nucleic acid manufacturing. Partner with us for innovative solutions that drive impactful results for your research. Explore how we can collaborate to elevate your projects! Visit us at https://wix.to/yKFzrD8 #Biotechnology #mRNA #ResearchInnovation

???????? ?????????????????? #??????-#?????? ??????????????? Researchers from Waters Corporation and Acuitas Therapeutics published a study on the impact of aldehyde content and impurities in lipid nanoparticles (LNPs) for #mRNA delivery. They found that the presence of aldehydes, particularly at higher concentrations, can lead to the formation of mRNA adducts, potentially decreasing the efficacy of mRNA therapeutics. Findings: ? 30% of tested samples exceeded the regulatory threshold for aldehyde content. ? RPLC-MS offers superior sensitivity and dynamic range compared to traditional detectors. ? Identified stability-indicating impurities and residual aldehydes in LNP raw materials. The findings suggest that monitoring aldehyde content and other impurities is crucial for ensuring the safety and efficacy of mRNA-based LNPs. The study highlights that traditional quality control measures may not fully capture the complexities of LNP formulations, underscoring the importance of advanced analytical techniques in the development of safe and effective therapeutics. ?????????????????? As noted by the authors, the presence of aldehydes and their potential to form adducts with mRNA raises concerns about the stability and effectiveness of LNPs. But it was very interesting to see that Lipid Vendors 8 and 9 showed low amounts of aldehyde content (Fig. 6) ?????? ?????????? ?????? ?????????????????????? ???????????? ?????????????????? (Fig. 7; 6-12% on day 7). This means that even a small portion of aldehydes <0.1% wt/wt can and will form these RNA-aldehyde adducts. The Question Remains: How much of the mRNA-LNP potency is actually reduced by the formation of these adducts? Read the article below ?? https://lnkd.in/e6uwZcDy

?? ???????? ???????????????? directly through the ???????? ?? A new study from the Gaurav Sahay lab demonstrates that intracameral (IC) administration of #LNPs enables #mRNA-driven gene expression and #CRISPR-based gene editing in the trabecular meshwork (TM)—a critical structure involved in glaucoma. ?? Key Findings: ?? LNP-mediated mRNA delivery successfully induced protein expression in the TM and corneal endothelium. ?? mCherry-mRNA LNPs showed peak expression at 72 hours, confirming efficient transfection. ?? Cas9-mRNA LNPs facilitated up to 14.3% in vivo gene editing in the iridocorneal angle. ?? No observable ocular toxicity post-injection, highlighting the safety of LNP-based gene therapies. ?? What This Means for Gene Therapy: These findings demonstrate a promising, non-viral approach to treating anterior eye diseases like glaucoma, which affects over 60 million people globally. By enabling precise gene expression and editing, LNPs may reduce the need for frequent eye-drop treatments and open new possibilities for long-lasting ocular gene therapies. ?? Some Thoughts: This study reinforces the growing role of LNPs as a non-viral alternative for gene therapy. Given that adeno-associated viruses (AAVs) face challenges like immunogenicity, cargo size limitations, and potential systemic spread, LNPs offer a more flexible and scalable alternative. Congratulations Aishwarya V. and Antony Jozic on the awesome work! Read the article below ?? https://lnkd.in/euFBF8VZ

?????????????????? is related to ???????????????? in mRNA-LNPs? Researchers from the Yvonne Perrie MBE lab at the University of Strathclyde recently published a study on the effects of citrate buffer molarity (50, 100, 300 mM) on lipid nanoparticles (#LNPs) for #mRNA delivery. They found that the emerging presence of extremely budded off bleb structures appear to decrease mRNA potency! Findings: ? Particle size increased slightly with higher citrate molarity. ? All formulations showed high encapsulation efficiency (>95%) and high mRNA recovery (>=95%). ? Higher molarity (300 mM) reduced cellular uptake and transfection efficiency in vitro and in vivo. ? Morphological changes included increased bleb structures at higher molarity, as shown by Cryo-TEM. The findings suggest that the molarity of the aqueous phase is crucial in determining the physicochemical properties and effectiveness of mRNA-based LNPs. The study emphasizes that common quality control attributes (e.g. size, polydispersity, and encapsualtion efficiency) may not adequately capture differences in formulations resulting from variations in manufacturing processes and buffer components, underscoring the importance of detailed characterization in LNP development. ???????????????? ?? As noted by the authors, there have been recent findings by Miffy Cheng and Pieter Cullis that showed bleb structures in mRNA-LNPs enhanced transfection properties in vitro and in vivo. This discrepancy highlights the complexity of LNP formulations and their interactions with biological systems. It suggests that the context of bleb formation—such as lipid composition, buffer conditions, and manufacturing methods—can significantly influence their functional outcomes. Thus, while blebs may enhance transfection in some scenarios, they could hinder it in others, emphasizing the need for a nuanced understanding of LNPs to optimize their design for specific applications. Read the article below ?? https://lnkd.in/ep-jmP7r

?? ?????????? ?????????????????????????????????? and ?????????? ?????????????????????????? ?? The Kurt Ristroph lab at Purdue University investigated how mixing factors during Flash NanoPrecipitation (FNP) affect polyelectrolyte-surfactant complexation and RNA lipid nanoparticles formation. ~~~~~~~~~~~~~~~~~~~~~ The study reveals that even minor fluctuations in flow rates can significantly affect the stability and morphology of these complexes, which are crucial for effective drug delivery systems. 1. Flow fluctuations as low as ±5% significantly impact complex formation. 2. Steady flow (as opposed to peristaltic fluctuating flow) conditions yield smaller lipid nanoparticles (132.7?nm vs. 75.6?nm) with greater RNA encapsulation efficiency (34.0?% vs. 82.8?%). 3. Syringe pumps can provide steady flow conditions to yield monodisperse particles with low polydispersity (<0.20) and high encapsulation efficiency (>80%). ?????????? ?????????????????????????????????? is a rapid self-assembly process used to produce uniformly sized nanoparticles by mixing a solute-containing stream with a nonsolvent under controlled turbulent conditions. FNP is particularly valuable in pharmaceutical, biomedical, and material science applications for creating nanoparticles optimized for drug delivery, diagnostics, and advanced material development. Read the research article below ??: https://lnkd.in/dYa3ztWH ~~~~~~~~~~~~~~~~~~~~~ Contact us at Helix Biotech to learn more about FNP and RNA-LNPs! #LNP #RNA #mRNA #HelixBiotech

?? ???????????????? ?????? ????????? Researchers from the Michael J Mitchell lab recently published in Nano Letters a study on peptide-functionalized lipid nanoparticles (pLNPs) designed for targeted mRNA delivery to the brain. This innovative approach utilizes click chemistry to enhance the transfection efficiency of mRNA in brain endothelial and neuronal cells, overcoming challenges posed by the blood-brain barrier. ?????? ????????????????????????? ?? Overcoming the difficulties of extrahepatic delivery is significant because traditional lipid nanoparticles (LNPs) often accumulate in the liver, limiting their therapeutic potential for targeting other tissues, such as the brain. Peptide-functionalized LNPs improve neuronal transfection by utilizing specific targeting peptides that enhance binding to receptors highly expressed on brain endothelial cells and neurons, facilitating more efficient crossing of the blood-brain barrier. This targeted approach leads to significantly higher transfection rates in neuronal cells compared to traditional methods, which often lack specificity and result in lower delivery efficiency. Additionally, the incorporation of peptides can enhance cellular uptake and endosomal escape, further increasing the effectiveness of mRNA delivery to neurons. ?? The findings suggest that these pLNPs could significantly improve therapeutic strategies for neurological disorders by effectively delivering mRNA while minimizing liver accumulation. ~~~~~~~~~~~~~~~~~~~~~~ For more details, check out the full article?below ?? https://lnkd.in/eYtjzNbg #Lipidnanoparticles #mRNA #brain #HelixBiotech

???? ?????? ?????????? ??????????????????????????—?????????????????? ?????????????? ???????? ???????????????? ?????????????? MIT Researchers recently published in ???????????? ?????????????????????????? about the use of deep learning AI to help facilitate LNP design and optimization. ?????? ???????????????? 1. Identification of two novel lipids, FO-32 and FO-35, with superior mRNA delivery efficiency. ?? 2. Enhanced extrahepatic delivery observed in both lung and muscle tissues compared to existing lipid formulations. 3. Validation of results through multiple in vivo murine and ferret experiments, confirming the lipids' therapeutic potential. ?? 4. Demonstration of the effectiveness of AI-driven approaches in optimizing lipid formulations for many potentially different therapies. 5. Highlighting the importance of incorporating diverse datasets to improve lipid candidate identification. ~~~~~~~~~~~~~~~ ?????? ????????????????????????? The findings highlight the effectiveness of using AI-driven approaches to optimize lipid formulations for mRNA delivery. The study underscores the critical role of discovering novel and improved lipids in advancing gene therapy pipelines. The incorporation of these approaches will undoubtedly result in significant time and cost savings for researchers. ? Congratulations to Jacob Witten and coworkers on a great article! Click the link below to read the article ?? https://lnkd.in/eHqKWkdk #LNP #lipidnanoparticles #mRNA #AI #deeplearning #genetherapy #RNAtherapetics