Table 2.
Current approaches for mRNA delivery of antibodies.
| Type of disease | Disease | Target | Antibodies expressed | Organism tested | Comments | References |
|---|---|---|---|---|---|---|
| Infectious Pathogen | Chikungunya | E2 glycoprotein | CHKV-24 (mRNA-1994) | Mouse, NHP, and humans. | First ever clinical trial for an mRNA-expressed bNAb. Pre-clinical data shows protection against infection upon mRNA administration and antibody expression. | Kose et al., 2019 and August et al., 2021 |
| HBV | HBV surface antigens | G12-scFv, G12-scFv-Fc, and G12-IgG | Mouse | The expression of these three antibodies upon I.V. injection of the mRNA to C57BL/6 mice led to long-term clearance of HBV antigens from circulation. | Chen et al., 2022 | |
| HIV | Envelope protein | VRC01 | Mouse | The I.V. mRNA administration led to over 170μg/mL of antibodies in BALB/c or BLT mice. | Pardi et al., 2017 | |
| BHK cells | The mRNA-expressed antibody exhibited neutralizing potency comparable to recombinant protein in vitro. | Thran et al., 2017 | ||||
| PGT121 | Sheep and NHP | There was a marked antibody expression upon aerosol delivery of the mRNA either as full-length or only heavy chain in the reproductive tract. | Lindsay et al., 2020 | |||
| N6, PGDM1400, and PGT121 | Mouse | The I.V. administration of the mRNA mixture led to the concomitant expression of scFv-Fc antibodies retaining neutralization potency in Tg32. | Narayanan et al., 2022 | |||
| Influenza A | Influenza A antigen | Human IgG anti-Influenza A | NHP | The I.V. infusion of improved LNP led to increased antibody expression from the mRNA cargo. | Sabnis et al., 2018 | |
| M2e and FcɣRIV | RiboBiFE | Mouse | The expression of bispecific nanobody (VHHs) with protective features against viral infection was reported upon I.T. administration of the mRNA in BALB/c and C57BL/6. | Van Hoecke et al., 2020 | ||
| Influenza B | HA | CR8033 | Mouse | The I.V. mRNA administration led to up to 2μg/mL of circulating antibody in Swiss-Albino mice. However, this therapy could not protect from lethal infection. | Thran et al., 2017 | |
| Rabies | G glycoprotein | S057 | Mouse | The I.M. injection of the mRNA led to the expression of the antibody as early as 2h in Swiss-Albino mice, which protected them from viral infection even as post-expsosure prophylaxis. | Thran et al., 2017 | |
| Pseudomonas aeruginosa | PsI (Biofilm component) | CAM003 | Mouse | The expression of this antibody as an hIgA1 protein was achieved upon I.V. administration of the mRNA. This therapy led to similar levels of protection as those reported for the recombinant protein in BALB/c mice. | Deal et al., 2023 | |
| Poxviruses | Enveloped virions (EV) and mature virions (MV) | c7D11 (anti-L1 MV), c8A (anti-B5 EV), and c6C (anti-A33 EV) | Rabbits | All three antibodies could be expressed concomitantly upon I.M. injection of the mRNA mix. However, based on empirical projections, the therapy in its current state was unlikely to protect against viral infection. | Mucker et al., 2022 | |
| RSV | Fusion glycoprotein | Secreted Palivizumab (sPali) and RSV-neutralizing VHH camelid antibody (RSVaVHH) | Mouse | The prophylactic I.T. administration of the mRNA to BALB/c mice reduced viral loads and prevented severe disease. | Tiwari et al., 2018 | |
| Salmonella enterica Typhimurium | O5-antigen of LPS | Sal4 | Mouse | The I.V. administration of the mRNA led to the expression of this antibody as an hIgA2, which protected BALB/c mice from infection to similar levels as those reported for the recombinant protein. | Deal et al., 2023 | |
| SARS-CoV-2 | Spike protein (RBD) | CB6 | Mouse | Testing of self-replicating mRNA I.N. administered. Exhibited protection against viral infection in BALB/c. | Li et al., 2021 | |
| HB27 | Mouse and Hamster | This antibody (not the mRNA-expressing therapy) is currently being tested in human trials. IV-administration of the mRNA led to long-term protection from infection in BALB/c mice and Syrian hamster. | Deng et al., 2022 | |||
| COV2-2832 and DH1041 | Hamster | The nebulized prophylactic administration of the mRNA significantly protected Syrian hamsters from SARS-CoV-2. | Vanover et al., 2022 | |||
| hACE | 3E8 | Hamster | This self-replicating mRNA I.N.-administered to Syrian hamster protected against Beta, Delta, Gamma, and Omicron variants. | Zhang et al., 2023 | ||
| Zika | Envelope protein | ZIKV-117 | Mouse | The pre- or post-exposure I.M. administration of self-amplifying mRNA to C57BL/6 protected from lethal dose. | Erasmus et al., 2020 | |
| Cancer | Non-hodgkin lymphoma | CD20 | Rituximab | Mouse | There was a significant deceleration or abolishment of tumor growth in NOD/SCID mice upon I.V. administration of the mRNA. | Thran et al., 2017 |
| Lymphoblastic leukemia | CD3 and tumor associated proteins (CLDN6, CLDN18.2, and EpCAM) | Three different RiboMAbs | Mouse | The I.V. administration of mRNA encoding for these bispecific ScFv to NSG mice cleared advanced tumor as effectively as the recombinant protein. | Stadler et al., 2017 | |
| Breast cancer | HER-2 (ERBB2) | Trastuzumab | Mouse | The I.V. injection to C57BL/6 mice of the mRNA led to high levels of expression of the antibody and a selective reduction of HER2-positive tumors, with improved survival. | Rybakova et al., 2019 | |
| Hepatocellular carcinoma | CCL2 and CCL5 | BisCCL2/5i | Mouse | The I.V. administration of the mRNA coding for this bispecific single-domain VH antibody led to long-term survival of CD57BL/6 and BALB/c mice with primary, colorectal, and pancreatic metastasized hepatocellular carcinoma. | Wang et al., 2021 | |
| Colon carcinoma | PD-1 and PD-L1 | XA-1 | Mouse | A marked expression of this bispecific antibody was seen upon I.V. injection of the mRNA coding in C57BL/6 and NOD/SCID mice. There was also a marked tumor growth inhibition of MC38 cells implanted to NOD/SCID mice. | Wu et al., 2021 | |
| PD-1 | Pembrolizumab | Mouse | The I.V. administration of the mRNA coding for this antibody effectively reduced intestinal tumor growth and improved C57BL/6 NOD/SCID mice survival. | Wu et al., 2022 | ||
| Acute myeloid leukemia and Subcutaneous melanoma | CD3 and B7H3 | B7 homolog 3 protein (B7H3 or CD276) and CD3 bispecific T-cell engaging (BiTE) antibody | Mouse | The I.V. adminstration of the mRNA coding for the BiTE antibody led to high levels of its expression, with extended half-life compared to the recombinant protein. This therapy also resulted in a marked and long-lived antitumor efficacy in NSG mice. | Huan et al., 2023 | |
| Toxins | Escherichia coli (O157:H7) | Shiga toxin 2 (Stx2) | VNA-Stx2 | Mouse | The mRNA expression of the VNA protected cell viability against Shiga Toxin 2 (Stx2) and can be expressed in CD1 mice. | Thran et al., 2017 |
| Clostridium botulinum | Botulinum neurotoxin serotype A (BoNTA) | VH domain-based neutralizing agent (VNA)-BonTA | Mouse | The mRNA-expressed VNA neutralized BoNTA in vitro to levels comparable to the recombinant protein and can be expressed in CD1 mice. | Thran et al., 2017 | |
| BoNTA, BoNTB, and BoNTE | Heterohexamer VHH | Mouse | The I.M. administration of the mRNA-expressing heterohexamer expressed efficiently and protected CD1 mice from lethal toxin doses for all serotypes of toxins tested. | Mukherjee et al., 2022 | ||
| BoNTA | B11-Fc | Mouse | The I.M. administration of the mRNA-expressing nanobody protected BALB/c mice from high lethal doses of serotype A toxin. | Panova et al., 2023 |