Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery

Zimmermann, Christoph M.; Baldassi, Domizia; Chan, Karen Y. T.; Adams, Nathan B. P.; Neumann, Alina; Porras-Gonzalez, Diana; Wei, Xin; Kneidinger, Nikolaus; Stoleriu, Mircea Gabriel; Burgstaller, Gerald; Witzigmann, Dominik; Luciani, Paola; Merkel, Olivia M.

doi:10.1016/j.jconrel.2022.09.021

Cited by 42 publications

(14 citation statements)

References 65 publications

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“…The LNPs consisted of an ionizable cationic lipid that is a sulfur-containing analog of DLin-MC3-DMA, a helper lipid, cholesterol, and PEG-DMG-encapsulating siRNA. The study verified the successful spray-drying procedure of LNP-siRNA systems while maintaining their integrity and mediating strong gene-silencing efficiency on mRNA and protein levels both in vitro and ex vivo [32].…”

Section: Applicationssupporting

confidence: 52%

Biodrug Delivery Systems: Do mRNA Lipid Nanoparticles Come of Age?

Puccetti

Schoubben

Giovagnoli

et al. 2023

IJMS

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As an appealing alternative to treat and prevent diseases ranging from cancer to COVID-19, mRNA has demonstrated significant clinical effects. Nanotechnology facilitates the successful implementation of the systemic delivery of mRNA for safe human consumption. In this manuscript, we provide an overview of current mRNA therapeutic applications and discuss key biological barriers to delivery and recent advances in the development of nonviral systems. The relevant challenges that LNPs face in achieving cost-effective and widespread clinical implementation when delivering mRNA are likewise discussed.

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Section: Applicationssupporting

confidence: 52%

Biodrug Delivery Systems: Do mRNA Lipid Nanoparticles Come of Age?

Puccetti

Schoubben

Giovagnoli

et al. 2023

IJMS

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“…These spray-dried particles also exhibited gene silencing on the gene Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) ex vivo in human lung tissues. 102 In treating nonalcoholic steatohepatitis, Yan and colleagues formulated a mannose-modified lipid nanoparticle encapsulating anti-HMGB1 siRNA to inhibit liver inflammation. The mannose-conjugated LNPs targeted liver macrophages via mannose receptors and knockdown the HMGB1 gene, which reduced inflammation and restored liver function in a NASH mouse model.…”

Section: Delivery Strategies For Sirna Therapy Currently Used Clinica...mentioning

confidence: 99%

Ongoing Clinical Trials of Nonviral siRNA Therapeutics

Narasipura,

VanKeulen-Miller,

et al. 2023

Bioconjugate Chem.

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Short interfering RNAs (siRNA) are a powerful class of genetic medicines whose clinical translation can be hindered by their suboptimal delivery properties in vivo.Here, we provide a clinically focused overview that summarizes ongoing siRNA clinical trials from the perspective of innovations in nonviral delivery strategies. More specifically, our review begins by highlighting the delivery barriers and physiochemical properties of siRNA that make it challenging to deliver it in vivo. We then provide commentary on specific delivery strategies, including sequence modification, siRNA ligand conjugation, and nanoparticle and exosomal packaging, each of which can be used to control the delivery of siRNA therapies in living systems. Last, we provide a summary table of ongoing siRNA clinical trials which also highlights the indication of use, target, and National Clinical Trial (NCT) number associated with each entry. In writing this review, our work aims to highlight the key challenges and strategies for effective nonviral siRNA delivery in vivo, while simultaneously summarizing information on ongoing clinical trials for siRNA therapy in humans.

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“…The stability of LNP is enhanced by cholesterol [ 159 ]. One of the biggest breakthroughs in this field is the liver-targeted delivery of siRNA by LNP [ 156 , 160 ]. The first liver-targeted siRNA-LNP drug, Onpattro® (Patisiran) has been approved by US FDA and European Medicines Agency [ 161 ].…”

Section: In Vivo Delivery Of Rlr-activating Rna By Nanoparticles Extr...mentioning

confidence: 99%

Exploiting RIG-I-like receptor pathway for cancer immunotherapy

et al. 2023

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RIG-I-like receptors (RLRs) are intracellular pattern recognition receptors that detect viral or bacterial infection and induce host innate immune responses. The RLRs family comprises retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2) that have distinctive features. These receptors not only recognize RNA intermediates from viruses and bacteria, but also interact with endogenous RNA such as the mislocalized mitochondrial RNA, the aberrantly reactivated repetitive or transposable elements in the human genome. Evasion of RLRs-mediated immune response may lead to sustained infection, defective host immunity and carcinogenesis. Therapeutic targeting RLRs may not only provoke anti-infection effects, but also induce anticancer immunity or sensitize “immune-cold” tumors to immune checkpoint blockade. In this review, we summarize the current knowledge of RLRs signaling and discuss the rationale for therapeutic targeting RLRs in cancer. We describe how RLRs can be activated by synthetic RNA, oncolytic viruses, viral mimicry and radio-chemotherapy, and how the RNA agonists of RLRs can be systemically delivered in vivo. The integration of RLRs agonism with RNA interference or CAR-T cells provides new dimensions that complement cancer immunotherapy. Moreover, we update the progress of recent clinical trials for cancer therapy involving RLRs activation and immune modulation. Further studies of the mechanisms underlying RLRs signaling will shed new light on the development of cancer therapeutics. Manipulation of RLRs signaling represents an opportunity for clinically relevant cancer therapy. Addressing the challenges in this field will help develop future generations of cancer immunotherapy.

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Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery

Cited by 42 publications

References 65 publications

Biodrug Delivery Systems: Do mRNA Lipid Nanoparticles Come of Age?

Biodrug Delivery Systems: Do mRNA Lipid Nanoparticles Come of Age?

Ongoing Clinical Trials of Nonviral siRNA Therapeutics

Exploiting RIG-I-like receptor pathway for cancer immunotherapy

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