In vivo fate and intracellular trafficking of vaccine delivery systems

Lee, Jaiwoo; Kim, Dong-Yoon; Byun, Junho; Wu, Yina; Park, Jin-Won; Oh, Yu‐Kyoung

doi:10.1016/j.addr.2022.114325

Cited by 35 publications

(21 citation statements)

References 189 publications

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“…The vast majority of FDA-approved biologics are delivered via injection, and operate within serum, on cell surfaces, or within endosomal vesicles. Those that do operate in the cytosol − notably achieve activity with endosomal escape efficiencies of 10% or lower. , The impact of biologic-based therapeutic strategies would expand exponentially if proteins and nucleic acids could reliably evade endosomal degradation, escape endosomal vesicles, and remain functional. Yet progress toward this goal has been exceptionally slow.…”

Section: Introductionmentioning

confidence: 99%

Dose-Dependent Nuclear Delivery and Transcriptional Repression with a Cell-Penetrant MeCP2

et al. 2023

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The vast majority of biologic-based therapeutics operate within serum, on the cell surface, or within endocytic vesicles, in large part because proteins and nucleic acids fail to efficiently cross cell or endosomal membranes. The impact of biologic-based therapeutics would expand exponentially if proteins and nucleic acids could reliably evade endosomal degradation, escape endosomal vesicles, and remain functional. Using the cell-permeant mini-protein ZF5.3, here we report the efficient nuclear delivery of functional Methyl-CpG-binding-protein 2 (MeCP2), a transcriptional regulator whose mutation causes Rett syndrome (RTT). We report that ZF-tMeCP2, a conjugate of ZF5.3 and MeCP2(Δaa13–71, 313–484), binds DNA in a methylation-dependent manner in vitro, and reaches the nucleus of model cell lines intact to achieve an average concentration of 700 nM. When delivered to live cells, ZF-tMeCP2 engages the NCoR/SMRT corepressor complex, selectively represses transcription from methylated promoters, and colocalizes with heterochromatin in mouse primary cortical neurons. We also report that efficient nuclear delivery of ZF-tMeCP2 relies on an endosomal escape portal provided by HOPS-dependent endosomal fusion. The Tat conjugate of MeCP2 (Tat-tMeCP2), evaluated for comparison, is degraded within the nucleus, is not selective for methylated promoters, and trafficks in a HOPS-independent manner. These results support the feasibility of a HOPS-dependent portal for delivering functional macromolecules to the cell interior using the cell-penetrant mini-protein ZF5.3. Such a strategy could broaden the impact of multiple families of biologic-based therapeutics.

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Section: Introductionmentioning

confidence: 99%

Dose-Dependent Nuclear Delivery and Transcriptional Repression with a Cell-Penetrant MeCP2

et al. 2023

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“…The intracellular trafficking and in vivo behavior and fate of vaccines administered via various routes and delivery systems have been recently reviewed [ 187 ]. In general, because of limited accessibility and/or inefficient cell permeation, most vaccine molecules are not efficiently recognized by the immune system and thus are susceptible to degradation.…”

Section: Concluding Remarks and Future Prospectsmentioning

confidence: 99%

“…In general, because of limited accessibility and/or inefficient cell permeation, most vaccine molecules are not efficiently recognized by the immune system and thus are susceptible to degradation. However, effective vaccine delivery systems should encompass protection from enzymatic degradation, improvement of pharmacokinetic properties through surface engineering strategies such as PEGylation, and sophisticated vaccine targeting and delivery strategies, as discussed in detail elsewhere [ 187 ]. Ferritin nanoparticles are remarkably stable, biocompatible, and amenable to genetic fusion and chemical conjugation, making the protein nanocage a very attractive platform for a wide range of biomedical applications, especially as an antigen display platform in the development of vaccines.…”

Section: Concluding Remarks and Future Prospectsmentioning

confidence: 99%

Ferritin nanocages as efficient nanocarriers and promising platforms for COVID-19 and other vaccines development

Reutovich

Srivastava

Arosio

et al. 2023

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…The lipid composition of the cellular membrane bilayer is the basis for designing and formulating the LNPs. The favorable interactions of the LNPs with the cell membrane determines the internalization, release, and stability of the payload ( Bunea et al, 2020 ; Lee et al, 2022 ). Currently, LNPs are a popular strategy being explored for various diseases and applications ( Chernikov et al, 2019 ), mostly attributable to the success of the mRNA-based vaccines against COVID-19.…”

Section: Nanoparticles (Nps) Used For the Sirna Therapy Of Covid-19mentioning

confidence: 99%

Potential of siRNA in COVID-19 therapy: Emphasis on in silico design and nanoparticles based delivery

Fopase

Panda

Rajendran

et al. 2023

Front. Bioeng. Biotechnol.

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Small interfering RNA (siRNA)-mediated mRNA degradation approach have imparted its eminence against several difficult-to-treat genetic disorders and other allied diseases. Viral outbreaks and resulting pandemics have repeatedly threatened public health and questioned human preparedness at the forefront of drug design and biomedical readiness. During the recent pandemic caused by the SARS-CoV-2, mRNA-based vaccination strategies have paved the way for a new era of RNA therapeutics. RNA Interference (RNAi) based approach using small interfering RNA may complement clinical management of the COVID-19. RNA Interference approach will primarily work by restricting the synthesis of the proteins required for viral replication, thereby hampering viral cellular entry and trafficking by targeting host as well as protein factors. Despite promising benefits, the stability of small interfering RNA in the physiological environment is of grave concern as well as site-directed targeted delivery and evasion of the immune system require immediate attention. In this regard, nanotechnology offers viable solutions for these challenges. The review highlights the potential of small interfering RNAs targeted toward specific regions of the viral genome and the features of nanoformulations necessary for the entrapment and delivery of small interfering RNAs. In silico design of small interfering RNA for different variants of SARS-CoV-2 has been discussed. Various nanoparticles as promising carriers of small interfering RNAs along with their salient properties, including surface functionalization, are summarized. This review will help tackle the real-world challenges encountered by the in vivo delivery of small interfering RNAs, ensuring a safe, stable, and readily available drug candidate for efficient management of SARS-CoV-2 in the future.

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In vivo fate and intracellular trafficking of vaccine delivery systems

Cited by 35 publications

References 189 publications

Dose-Dependent Nuclear Delivery and Transcriptional Repression with a Cell-Penetrant MeCP2

Dose-Dependent Nuclear Delivery and Transcriptional Repression with a Cell-Penetrant MeCP2

Ferritin nanocages as efficient nanocarriers and promising platforms for COVID-19 and other vaccines development

Potential of siRNA in COVID-19 therapy: Emphasis on in silico design and nanoparticles based delivery

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