Table 2.
Prototypical clinical trials of LNP-based nucleic acid delivery systems.
| LNP-based nucleic acid delivery systems for cancer therapy | |||||||
|---|---|---|---|---|---|---|---|
| Clinical Trials | Phase | Disease | Interventions | Route | Sponsor | ||
| NCT00882180 | Phase I | Solid tumors | siRNA against VSP/VEGF-A | Intravenous infusion | Alnylam Pharma | ||
| NCT01262235 | Phase I/II | Gastrointestinal Neuroendocrine Tumors | siRNA against PLK1 | Intravenous infusion | Arbutus Biopharma | ||
| NCT02191878 | Phase I/II | Hepatocellular carcinoma | siRNA against PLK1 | Intravenous infusion | Arbutus Biopharma | ||
| NCT03323398 | Phase I/II | Relapsed/Refrac tory Solid Tumor Malignancies or Lymphoma | mRNA-2416 encoding OX40L, alone (Phase I) or in combination with i.v. PD- L1 inhibitor, Durvalumab (Phase 2) | Intratumoral | Moderna TX, Inc. | ||
| NCT03323398 | Phase I | Advanced/metas tatic solid tumors or lymphoma | mRNA encoding human OX40L | Intratumoral | Moderna TX, Inc., | ||
| NCT03313778 | Phase I | Solid tumors | mRNA encoding for personalized neoantigens | Intramuscul ar | ModernaT X, Inc., | ||
| NCT02340156 | Phase II | Recurrent glioblastoma | Plasmid vector encoding wild- type p53 DNA (+temozolomi de) | Intravenous infusion | SynerGene | ||
| NCT01505153 | Phase I | Advanced and/or metastatic Cancer | Plasmid vector encoding shRNAs against STMN1 | Intratumoral | Strike Bio | ||
| NCT02716012 | Phase I | Advanced liver cancer | small activating RNA to activate the CEPBA gene | Intravenous infusion | Mina Alpha | ||
| NCT02410733 | Phase I | Melanoma | Four mRNAs encoding melanoma- associated antigens (MAAs) | Intravenous infusion | BioNTech | ||
| NCT02316457 | Phase I | Triple negative breast cancer | mRNAs encoding tumour- associated antigens (TAAs) and/or personalized neoantigens | Intravenous infusion | BioNTech | ||
| NCT01808638 | Phase Ib/Iia | Advanced or metastatic pancreatic cancer | siRNA against PKN3 (+ gemcitabin e) | Intravenous infusion | Silence Therapeuti cs GmbH | ||
| NCT03739931 | Phase I | Metastatic disease | mRNA-2752- OX40L, IL-23, and IL-36γ mRNA with LNPs and Durvalumab | Intratumoral | Moderna TX, Inc | ||
| NCT01591356 | Phase I | Advanced cancers | siRNA against EphA2 | Intravenous infusion | M.D. Anderson Cancer Center | ||
| LNP-based nucleic acid therapies for systemic diseases | |||||||
| Clinical Trials | Phase | Disease | Interventions | Route of immunizati on | Sponsor (s) | ||
| NCT04601051 | Phase I | Familial Amyloid Polyneuropathy, Transthyretin- Related Familial Amyloid Cardio- myopathy, Wild- Type Transthyretin Cardiac Amyloidosis | NTLA-2001- CRISPR-Cas9 system delivers by LNPs | intravenous | Intellia | ||
| NCT05398029 | Phase1b | CRISPR base-editing medicine to PCSK9 gene turn off | VERVE-101 | intravenous | Verve | ||
| hepatic protein production for heart disease | |||||||
| NCT03767270 | Phase I/2 | Ornithine Transcarbamylase Deficiency | MRT5201-human ornithine transcarbamyl-ase mRNA with lipid- based nanoparticles | intravenous | Translate Bio, Inc. | ||
| NCT04159103 | Phase I/2 | Propionic acidaemia | mRNA-3927 encoding Propionyl- CoA carboxylase | intravenous | Moderna TX, Inc. | ||
| NCT03375047 | Phase I/2 | Cystic fibrosis | MRT5005 | Inhalation | Translate Bio, Inc. | ||
LNPs are a successful delivery vehicle that allow for improved treatment outcomes for vaccines and therapies. This includes treatment and prevention for a broad range of genetic, infectious, and cancerous diseases. Clinical trials for cytotoxic chemotherapy agents, antibiotics, and nucleic acid therapeutics are outlined in this table. LNP-based COVID-19 mRNA vaccines from Pfizer/BioNTech and Moderna were successfully developed with international impact.