Table 3.
Nuclei Acid Candidate | Clinical Trial study ID (NCT) | Phase | Formulation/Description | Lipid Composition | Disease/Conditions | Route of Administration | Ref. | Sponsor | Status |
---|---|---|---|---|---|---|---|---|---|
mRNA-LNP | |||||||||
Cancer | |||||||||
mRNA-2752/ Durvalumab | NCT03739931 | Phase 1 (2018–2026) | Novel mRNA-based therapeutic agent encoding OX40L T cell co-stimulator, IL-23 and IL-36γ pro-inflammatory cytokines |
DLin-MC3-DMA, DSPC, Cholesterol, DSPE-PEG2000 | Relapsed/refractory solid tumor malignancies or lymphoma | Intratumoral | (Deng et al., 2022; Manish et al., 2021) | ModernaTX, Inc. | Active, Not Recruiting |
MEDI1191/Durvalumab | NCT03946800 | Phase 1 (2019–2023) | LNP formulation therapy of IL-12 mRNA to induce a potent TH1-mediated anti-tumor response | N/A | Solid Tumors | Intratumoral/IV | (Hamid et al., 2021) | MediImmune LLC | Completed |
mRNA-4157/Pembrolizumab |
NCT03313778 NCT03897881 |
Phase 1 (2017–2025) Phase 2 (2019–2029) |
LNP-encapsulated mRNA-4157 that encodes 34 different patient-specific neoantigens in combination with Pembrolizumab |
N/A | Solid tumors including melanoma, bladder carcinoma, HPV-neg HNSCC, NSCLC, SCLC, MSI-high, TMB-high cancers | IM/IV | (Burris et al., 2019; Julie et al., 2020; Weber et al., 2024) | ModernaTX, Inc. | Recruiting |
SAR441000 | NCT03871348 | Phase 1 (2019–2024) | A mixture of four mRNAs encoding IL-12sc, IFN-α-2b, GM-CSF and IL-15sushi as monotherapy and in combination with cemiplimab | N/A | Advanced solid tumors | Intratumoral/IV | (Oliver et al., 2020) | Sanofi | Active, Not recruiting |
mRNA-2416 | NCT03323398 | Phase1/2 (2017-2021) | LNP-encapsulated mRNA encoding human OX40L alone or in combination with Duvulamab | N/A | Relapsed/Refractory Solid Tumor Malignancies or Lymphoma and Ovarian Cancer | Intratumoral | (Jimeno et al., 2020) | ModernaTX, Inc. | Terminated |
mRNA-5671/ V941 and Pembrolizumab | NCT03948763 | Phase 1 (2019–2022) | LNP-encapsulated mRNA-5671 that encodes for most common KRAS substitutions (G12d, G12V, G13D, G12C) either alone or in combination with Pembrolizumab | N/A | Neoplasms | IM/IV | (Barbier et al., 2022) | Merck Sharp & Dohme LLC | Completed |
NCI-4650 | NCT03480152 | Phase 1/2 (2018–2019) | A mRNA based personalized cancer vaccine that targets up to 15 tumor-associated antigens | N/A | Melanoma, Colon Cancer, Gastrointestinal Cancer, Genitourinary cancer, hepatocellular cancer | IM | (Cafri et al., 2020) | National Cancer Institute | Terminated |
Cardiovascular disease | |||||||||
mRNA-0184 | NCT05659264 | Phase 1 (2022–2025) | LNP-encapsulated mRNA-0184 that encodes for relaxin hormone | N/A | Chronic Heart Failure | IV | (Soroudi et al., 2024) | ModernaTX, Inc. | Recruiting |
Viral diseases/Influenza | |||||||||
mRNA-1345/ Afluria®Quadrivalent/mRNA-1273.214 | NCT05330975 | Phase 3 (2022–2024) | mRNA-1345 co-administered with seasonal influenza vaccine (Afluria) to evaluate the impact of co-administration on immune respose of RSV-A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) | N/A | Respiratory Syncytial Virus in adults over 50 and SARS-COV2 | IM | (Li et al., 2023; Wilson et al., 2023) | ModernaTX, Inc. | Active, not recruiting |
mRNA-1345 | NCT05127434 | Phase 2/3 2021–2025 |
LNPs with encapsulated mRNA encoding for a stabilized prefusion F glycoprotein | N/A | Respiratory Syncytial Virus (RSV) | IM | Moderna TX, Inc | Active, not recruiting | |
mRNA-1273 mRNA-1010 mRNA-1345 mRNA −1647 FLUAD® |
NCT05397223 | Phase 1 (2022–2026) | LNPs encapsulating mRNA-1273, mRNA-1010, mRNA-1345, and mRNA-1647 to observe systemic reactogenicity, adverse effects and adverse reactions | N/A | Respiratory Syncytial Virus in healthy adults, SARS-CoV-2, Cytomegalovirus | IM | (Lee et al., 2023a) | ModernaTX, Inc. | Active, not recruiting |
mRNA-1273 mRNA-1273.351 |
NCT04405076 | Phase 2 (2020−2021) | LNP-encapsulated mRNA-1273 vaccine encoding a pre-fusion stabilized form of the SARS-CoV-2 spike protein (S—2P). | N/A | SARS-COV-2 Booster dose |
IM | (Choi et al., 2021) | ModernaTX, Inc. | Completed |
Spikevax mRNA-1273 |
NCT04283461 NCT04470427 |
Phase 1 (2020−2022) Phase 3 (2020–2022) |
LNP-mRNA-1273 is a lipid-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized spike (S) protein of SARS-CoV-2 | SM-102, and 3 commercially available lipids, cholesterol, DSPC, and PEG2000 DMG. | SARS-CoV-2 | IM | (Baden et al., 2021) | National Institute of Allergy and Infectious Diseases (NIAID) | Completed |
mRNA-1283 | NCT05137236 | Phase 2 (2021−2023) | Next generation SARS-CoV2 vaccine composed of LNP encapsulated mRNA-1283 | N/A | SARS-CoV-2 | IM | (Yassini et al., 2023) | ModernaTX, Inc. | Completed |
Comirnaty (BNT162b2) | NCT04368728 | Phase 1/2/3 (2020−2023) | LNP-encapsulated nucleoside-modified mRNA that encodes membrane-anchored, full-length SARS-CoV-19 S-protein | ALC-0315, ALC-0519, DSPC Cholesterol | SARS-CoV-2 | IM | (Polack et al., 2020b) (Lamb, 2021) | BioNTech SE | Completed |
CV-NCOV | NCT04449276 | Phase 1 (2020–2021) | LNP-formulated SARS-CoV-2 vaccine containing mRNA encoding perfusion conformation-stabilized full-length SARS-CoV-2 spike protein | DSPC, cationic lipid, PEG-lipid conjugate, cholesterol | SARS-CoV-2 | IM | (Kremsner et al., 2021) | CureVac | Completed |
ARCoV | NCT04847102 | Phase 3 (2021–2023) | mRNA-LNP that encodes the receptor binding domain of the S-protein of SARS-CoV2 | Ionizable lipid (Lipid 9001), (1,2-DSPC, cholesterol and PEG-lipid | SARS-CoV-2 | IM | (Zhang et al., 2020a) (Chen et al., 2022) | Walvax Biotechnology Co., Ltd. | Unknown Status |
mRNA-1010 | NCT04956575 | Phase 1/2 (2021−2022) | LNP encapsulating quadrivalent seasonal influenza vaccine encoding membrane-bound HA surface glycoproteins of four influenza strains (A/H1N1, A/H3N2, B/Victoria, and B/Yamagata) recommended by the WHO for cell- or recombinant vaccines | N/A | Seasonal influenza A: H1N1 and H3N2 Influenza B: strains including Victoria-lineage and Yamagata lineage |
IM | (Lee et al., 2023a) | ModernaTX, Inc. | Completed |
mRNA −1647 mRNA-1443 |
NCT03382405 |
Phase 1 (2017–2020) |
LNP encapsulated mRNA-1647 comprises six mRNAs encoding for CMV antigens given along with LNP-encapsulated mRNA-1443 encoding pp65 from T cells of the CMV antibody |
N/A | Cytomegalovirus (CMV) | IM | (Jung et al., 2022) | ModernaTX, Inc. | Completed |
mRNA-1647 | NCT04232280 | Phase 2 (2020–2023) | LNP encapsulating mRNA-1647 cytomegalovirus vaccine in CMV-seronegative and CMV-seropositive healthy adults | N/A | IM | (Panther et al.) | Completed | ||
NCT05085366 | Phase 3 (2021–2026) | Active, not recruiting | |||||||
mRNA-1653 | NCT04144348 | Phase 1 (2019–2022) | LNP encapsulated bivalent vaccine comprised of nucleoside-modified mRNA encoding full-length membrane-bound fusion proteins of hMPV and PIV3 | N/A | Human Metapneumovirus and Human parainfluenza virus | IM | (August et al., 2022; Nelson et al., 2020; Schnyder Ghamloush et al., 2024) | ModernaTX, Inc. | Completed |
mRNA-1440 (VAL-506440) | NCT03076385 | Phase 1 (2015–2018) | LNP-formulated modified mRNA-based vaccine encoding hemagglutinin (HA)proteins of H10N8 or H7N9 influenza strain | N/A | Influenza A (H10N8 and H7N9) | IM | (Bahl et al., 2017; Feldman et al., 2019) | ModernaTX, Inc. | Completed |
mRNA-1851 (VAL-339851) | NCT03345043 | Phase 1 (2016–2018) | LNP encapsulated mRNA-1851 that encodes for the HA protein of H7N9 | N/A | Influenza A virus H7N9 subtype | IM | (Shi et al., 2022) | ModernaTX, Inc. | Completed |
CV7202 | NCT03713086 | Phase 1 (2018–2021) | RABV-G mRNA using initial formulation CV7201 antigen with cationic protein protamine encapsulated in LNP | Ionizable amino lipid, DSPC, PEG-2000-DMG, Cholesterol | Rabies virus glycoprotein (RABV-G) | IM | (Aldrich et al., 2021; Shi et al., 2022) | CureVac | Completed |
mRNA-1325 | NCT03014089 | Phase 1 (2016–2019) | LNP-encapsulated modified mRNA vaccine encoding premembrane and envelope E structural proteins (prME) from a Micronesia 2007 Zika virus isolate | Proprietary ionizable lipids, DSPC, cholesterol, and PEG-lipid | Zika Virus | IM | (Richner et al., 2017) (Bollman et al., 2023) | ModernaTX, Inc. | Completed |
mRNA-1944 | NCT03829384 | Phase 1 (2019–2021) | LNP-encapsulated mRNA-1944 that encodes for the heavy and light chains of CHKV-24 antibody | Proprietary high purity PEG-2000 stearate monoester, IAL (proprietary ionizable amino lipid), cholesterol, DSPC | Chikungunya virus | IV | (August et al., 2021) | ModernaTX, Inc. | Completed |
mRNA-1893 | NCT04917861 | Phase 2 (2021–2024) | LNP-encapsulated mRNA-1893 vaccine encoding the envelope E structural proteins (prME) from the RIO-U1 Zika virus isolate | Proprietary ionizable lipid, DSPC, cholesterol, and PEG lipid | Zika virus | IV | (Bollman et al., 2023; Essink et al., 2023; Li et al., 2024) | ModernaTX, Inc. | Active, not recruiting |
mRNA-1215 | NCT05398796 | Phase 1 (2022–2024) | LNP encapsulated mRNA-1215 that encodes for Nipah perfusion F protein and G protein | N/A | Nipah Virus (NiV) Infection | IM | (Rodrigue et al., 2024; Wang et al., 2023c) | ModernaTX, Inc. | Active, not recruiting |
H1ssF-3928 |
NCT03814720 NCT05755620 |
Phase 1 (2019–2021) Phase 1 (2023–2025) |
VRC H1ssF 3928 mRNA-LNP vaccine encoding influenza H1 hemagglutinin stem | N/A | Influenza | IM | (Andrews et al., 2023; Widge et al., 2023) | National Institute of Allergy and Infectious Diseases (NIAID) | Completed Recruiting |
DCVC H1 HA | NCT05945485 | Phase 1 (2023–2024) | mRNA-LNP vaccine encoding full length H1 HA of influenza A/California/07/2009 (H1N1) | N/A | Influenza A/H1N1 | IM | National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting | |
AVX502 | NCT00440362 | Phase 1/2 (2007) | Alphavirus Replicon Vaccine Expressing Influenza HA protein | N/A | Influenza | IM/SC | AlphaVax, Inc. | Completed | |
mRNA-1189 | NCT05164094 | Phase 1 (2021–2025) | LNP-encapsulated mRNAs that encode Epstein-Barr Virus (EBV) envelope glycoproteins gp42, gp220, gH and gL | N/A | Epstein-Barr Virus (EBV) | IM | (Zhong et al., 2022) | ModernaTX, Inc | Active, Not Recruiting |
Genetic disorders | |||||||||
mRNA-3704 | NCT03810690 | Phase 1/2 (2019–2020) | LNP-encapsulated mRNA encoding human methylmalonyl-CoA mutase (hMUT) | N/A | Methylmalonic acidemia | IV | (Hou et al., 2021) | ModernaTX, Inc. | Withdrawn |
mRNA-3705 | NCT05295433 | Phase 1/2 (2022–2034) | LNP-encapsulated mRNA encoding hMUT | SM-86, DSPC, cholesterol, and OL-56 [polyethylene glycol-lipid conjugate] | Methylmalonic Acidemia | IV | (Baek et al., 2024; Suzuki et al., 2023) | ModernaTX, Inc | Recruiting |
mRNA-3927 |
NCT04159103 NCT05130437 |
Phase1/2 (2021−2031) | LNP-encapsulated dual mRNA therapy that encodes for (propionic-CoA mutase) PCC-A and PCC-B subunit proteins restoring PCC enzyme in liver | SM-86, DSPC, cholesterol, and OL-56 [polyethylene glycol-lipid conjugate] | Propionic Acidemia | IV | (Attarwala et al., 2023; Baek et al., 2024) | ModernaTX, Inc. | Recruiting |
MRT5201 | NCT03767270 | Phase 1/2 (2019–2022) | LNP-encapsulated codon-optimized human OTC mRNA | N/A | Ornithine Transcarbamylase Deficiency | IV | Translate Bio, Inc. | Withdrawn | |
MRT5005 | NCT03375047 | Phase 1/2 (2018–2021) | Aerosolized LNP-encapsulated a codon-optimized CFTR mRNA | N/A | Cystic Fibrosis | Nebulization | (Barbier et al., 2018; Hou et al., 2021; Rowe et al., 2023) | Translate Bio, Inc. | Unknown Status |
ARCT-810 | NCT04442347 | Phase 1 (2020–2023) | Human ornithine transcarbamylase (hOTC) mRNA-LNP | N/A | Ornothine Transcarbamylase Deficiency | IV | (Yamazaki et al., 2023) | Arcturus Therapeutics, Inc. | Active, not recruiting |
NCT05526066 | Phase 2 (2022–2024) | Recruiting | |||||||
siRNA | |||||||||
ALN-TTR01 | NCT01148953 | Phase 1 (2010−2012) | First gen formulation of LNPs to deliver siRNAs | DLin-MC3- DMA, DSPC, PEG2000-C-DMG, Cholesterol | Transthyretin (TTR) Mediated amyloidosis (ATTR) | IV | (Coelho et al., 2013; Schoenmaker et al., 2021a; Zatsepin et al., 2016) | Alnylam Pharmaceuticals | Completed |
ALN-TTR02 | NCT01559077 | Phase 1 (2012) | Second gen formulation of LNPs to deliver siRNAs | DLin-MC3- DMA, DSPC, PEG2000-C-DMG, Cholesterol | Transthyretin (TTR) Mediated amyloidosis (ATTR) | IV | (Adams et al., 2018; Coelho et al., 2020; Coelho et al., 2013; Schmidt et al., 2022; Suhr et al., 2015; Zatsepin et al., 2016) | Alnylam Pharmaceuticals | Completed |
NCT01617967 | Phase 2 (2012–2014) | Completed | |||||||
NCT01961921 | Phase 2 (2013–2016) | Completed | |||||||
NCT01960348 | Phase 3 (2013–2017) | Completed | |||||||
NCT03862807 | Phase 3 (2019–2020) | Completed | |||||||
NCT02510261 | Phase 3 (2015–2022) | Completed | |||||||
DCR-MYC | NCT02110563 | Phase 1 (2014–2016) | DCR-MYC is a LNP-formulated Dicer substrate siRNA (DsiRNA) that silences MYC mRNA | N/A | Solid tumors, multiple myeloma, non-Hodgkins lymphoma | IV | (Chipumuro et al., 2016; Tolcher et al., 2015) | Dicerna Pharmaceuticals | Terminated |
NCT02314052 | Phase 1/2 (2015–2016) | Hepatocellular carcinoma | Terminated | ||||||
ND-L02-s0201 | NCT01858935 | Phase 1 (2013–2014) | LNP-encapsulated anti- hsp47 siRNA formulation designed to reversibly inhibit the expression of HSP47 | Six key lipid components including cationic, helper and targeting lipids (names of lipids not specified) | Safety, Tolerability and Pharmacokinetics in Healthy Normal Subjects | IV | (Liu et al., 2021) | Bristol-Myers Squibb | Completed |
NCT02227459 | Phase 1/2 (2014–2016) | Moderate to Extensive Hepatic Fibrosis | Bristol-Myers Squibb | Completed | |||||
NCT03538301 | Phase 2 (2018–2022) | Idiopathic Pulmonary Fibrosis | Nitto Denko Corporation | Completed | |||||
TKM-080301 | NCT01437007 | Phase 1 (2011−2012) | LNP containing siRNA against PLK1 gene products | Four lipid components | Hepatocellular carcinoma | Intra-arterial /IV | (Ramanathan et al., 2013) | National Cancer Institute (NCI) | Completed |
NCT01262235 | Phase 1/2 (2010–2015) | Adrenocortical carcinoma | (Demeure et al., 2016) | Arbutus Biopharma Corporation | Completed | ||||
NCT02191878 | Phase 1/2 (2014–2016) | Hepatocellular carcinoma | (El Dika et al., 2019) | Arbutus Biopharma Corporation | Completed | ||||
NBF-006 | NCT03819387 | Phase 1 (2019–2024) | LNP encapsulating siRNA targeting glutathione-S-transferase Pi | N/A | NSCLC, Pancreatic, Colorectal cancer | IV | (Hattab et al., 2021) | Nitto BioPharma., | Completed |
BMS-986263 | NCT03142165 | Phase 1 (2017) | BMS-986263, a retinoid-conjugated lipid nanoparticle delivering small interfering RNA designed to target heat shock protein (HSP)-47 mRNA, for the treatment of advanced fibrosis. | N/A | Hepatic Cirrhosis -Hepatic Impairment | IV | (Qosa et al., 2023a; Qosa et al., 2023b) | Bristol-Myers Squibb | Completed |
NCT03420768 | Phase 2 (2018–2019) | Completed | |||||||
NCT04225936 | Phase 1 (2020–2021) | Completed | |||||||
NCT04267393 | Phase 2 (2021–2024) | Terminated | |||||||
CRISPR/Cas9 (sgRNA) | |||||||||
NTLA-2001 |
NCT04601051 NCT06128629 |
Phase 1 (2020–2026) Phase 3 (2023–2028) |
LNP-encapsulated single guide RNA (sgRNA) targeting human TTR and a human-codon optimized mRNA sequence of S. pyogens Cas9 protein | N/A | Transthyretin (ATTR) amyloidosis with cardiomyopathy | IV | (Gillmore et al., 2021) | Intellia Therapeutics | Active, not recruiting Recruiting |
VERVE-101 | NCT05398029 | Phase 1 (2022–2024) | LNPs for a CRISPR-based gene editing that inactivates the PCSK9 gene | N/A | Heterozygous Familial Hypercholesteremia and Cardiovascular Disease | IV | (Lee et al., 2023b) | Verve Therapeutics | Recruiting |
VERVE-102 | NCT06164730 | Phase 1 (2024–2026) | LNP-encapsulated CRISPR-based treatment using a guide RNA targeting PCSK-9 gene | N/A | Heterozygous Familial Hypercholesteremia or Premature Coronary Artery Disease | IV | Verve Therapeutics | Not yet recruiting |