Since the approval of the lipid nanoparticles(LNP)-mRNA vaccines against the SARS-CoV-2 virus,there has been an increased interest in the delivery of mRNA through LNPs.However,current LNP formulations contain PEG lipi...Since the approval of the lipid nanoparticles(LNP)-mRNA vaccines against the SARS-CoV-2 virus,there has been an increased interest in the delivery of mRNA through LNPs.However,current LNP formulations contain PEG lipids,which can stimulate the generation of anti-PEG antibodies.The presence of these antibodies can potentially cause adverse reactions and reduce therapeutic efficacy after administration.Given the widespread deployment of the COVID-19 vaccines,the increased exposure to PEG may necessitate the evaluation of alternative LNP formulations without PEG components.In this study,we investigated a series of polysarcosine(pSar)lipids as alternatives to the PEG lipids to determine whether pSar lipids could still provide the functionality of the PEG lipids in the ALC-0315 and SM-102 LNP systems.We found that complete replacement of the PEG lipid with a pSar lipid can increase or maintain mRNA delivery efficiency and exhibit similar safety profiles in vivo.展开更多
文摘Since the approval of the lipid nanoparticles(LNP)-mRNA vaccines against the SARS-CoV-2 virus,there has been an increased interest in the delivery of mRNA through LNPs.However,current LNP formulations contain PEG lipids,which can stimulate the generation of anti-PEG antibodies.The presence of these antibodies can potentially cause adverse reactions and reduce therapeutic efficacy after administration.Given the widespread deployment of the COVID-19 vaccines,the increased exposure to PEG may necessitate the evaluation of alternative LNP formulations without PEG components.In this study,we investigated a series of polysarcosine(pSar)lipids as alternatives to the PEG lipids to determine whether pSar lipids could still provide the functionality of the PEG lipids in the ALC-0315 and SM-102 LNP systems.We found that complete replacement of the PEG lipid with a pSar lipid can increase or maintain mRNA delivery efficiency and exhibit similar safety profiles in vivo.
