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Cited by 166RNA Interference and Gene DeliveryImmunotherapy and Immune ResponsesMonoclonal and Polyclonal Antibodies Research

The DOI matches its Crossref record; 55 of the 56 references it cites were found in a registry or an index; 24 of the 49 sources its claims cite were checked for support.

mRNA mediates passive vaccination against infectious agents, toxins, and tumors

Open access
Thran, Moritz, Mukherjee, Jean, Pönisch, Marion, Fiedler, Katja, Thess, Andreas, Mui, Barbara L, Hope, Michael J, Tam, Ying K, Horscroft, Nigel, Heidenreich, Regina, Fotin‐Mleczek, Mariola, Shoemaker, Charles B, Schlake, Thomas·2017·EMBO Molecular Medicine
DOI 10.15252/emmm.201707678PMC PMC5623855
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Abstract

The delivery of genetic information has emerged as a valid therapeutic approach. Various reports have demonstrated that mRNA, besides its remarkable potential as vaccine, can also promote expression without inducing an adverse immune response against the encoded protein. In the current study, we set out to explore whether our technology based on chemically unmodified mRNA is suitable for passive immunization. To this end, various antibodies using different designs were expressed and characterized in vitro and in vivo in the fields of viral infections, toxin exposure, and cancer immunotherapies. Single injections of mRNA–lipid nanoparticle (LNP) were sufficient to establish rapid, strong, and long‐lasting serum antibody titers in vivo , thereby enabling both prophylactic and therapeutic protection against lethal rabies infection or botulinum intoxication. Moreover, therapeutic mRNA‐mediated antibody expression allowed mice to survive an otherwise lethal tumor challenge. In conclusion, the present study demonstrates the utility of formulated mRNA as a potent novel technology for passive immunization.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

Chemically unmodified mRNA in lipid nanoparticles encoding antibodies or VHH-based neutralizing agents produced rapid, protective serum titers in mice against rabies, botulinum toxin, and a lymphoma tumor challenge. The paper proposes mRNA as a flexible platform for passive immunization, with efficacy in both pre- and post-exposure settings.

Key findings

  • Single intravenous mRNA-LNP injections produced antibody serum titers detectable by 2 h, peaking at 6–12 h for anti-rabies mAb, with an estimated serum half-life of about 1 week; VNA serum half-lives were 24–36 h. Highest mAb levels were in the low two-digit μg/ml range, while VNA-BoNTA titers were about 20-fold higher than mAbs.
  • mRNA encoding anti-rabies mAb protected all mice when given 24 h before or 2 h after a lethal 5 × LD50 intramuscular rabies challenge; control mice receiving anti-influenza mAb mRNA mostly succumbed. In a second post-exposure study, 40 μg mRNA gave full protection, a fourfold lower dose gave partial protection, and buffer controls all died.
  • In botulinum intoxication, treatment with mRNA-LNP encoding VNA-BoNTA or recombinant VNA-BoNTA at 2 or 4 h after 4 × LD50 BoNT/A gave full survival with no clinical signs; at 6 h mice survived but showed moderate clinical signs, while VNA-Stx2 mRNA controls died within 36 h.
  • In a Raji Luc tumor model, repeated rituximab mRNA-LNP doses of 50 or 10 μg strongly decelerated or abolished tumor growth; all high-dose animals and all but two low-dose animals survived to day 28, whereas untreated controls were euthanized about 17 days after inoculation.

Methods

  • Proof-of-principle preclinical mouse study using chemically unmodified mRNA encoding IgG mAbs (anti-rabies S057/CR57, anti-influenza B CR8033, anti-HIV VRC01, rituximab) or VHH-based VNAs (anti-BoNT/A, anti-Stx2), formulated in lipid nanoparticles and administered intravenously; heavy- and light-chain mRNAs were mixed at approximately 1.5:1.
  • In vitro expression and function were tested in BHK, HepG2, primary mouse hepatocytes, HeLa, Raji, Vero, and reporter cells; in vivo studies used NIH Swiss albino, CD1, BALB/c, and NOD/SCID mice, with challenge models for rabies (5 × LD50 IM), BoNT/A (4 × LD50 IV), and Raji Luc lymphoma (2 × 10^6 cells IV).
  • Analyses included Western blot, IgG- or antigen-specific ELISA, FACS, rabies FAVN neutralization, HIV Magi R5-tropic entry assay, SNAP25 cleavage inhibition, Stx2 toxicity assay, whole-body luminescence imaging, survival monitoring, and GraphPad Prism statistics; ADA correlation used two-tailed nonparametric Spearman correlation.

Limitations

  • The paper states that applicability will have to be confirmed case-by-case; rabies will probably require intramuscular administration, and it remains to be demonstrated that this route enables protective expression levels. It also notes that the constructs used a fixed, previously approved mRNA design rather than individually optimized mRNAs, likely explaining differences in peak expression.
  • The paper reports that about half of mice receiving anti-rabies mAb showed accelerated serum clearance after about 2 weeks, correlating with anti-drug antibody responses attributed to the mismatch between humanized antibody sequence and mouse species, not to mRNA per se.
  • Evident from the text: all efficacy data are from mouse models, with no human data; challenge studies used small groups (e.g., 6–12 mice per group), and control survival in rabies experiments varied from 0% to 40%, which the authors interpret as natural variation under the challenge conditions.

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Integrity signals

Registry

Crossref · 10.15252/emmm.201707678

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

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Figures

Figure 1 In vitro expression of mRNA‐encoded antibodies mRNA design to encode heavy‐chain‐only VH domain (VHH)‐based neutralizing agents (VNAs). VNAs were supplemented by affinity E‐tags (Tag) and an albumin‐binding peptide (ABP).Western blot analysis of VNA‐BoNTA expression in cell lysates and supernatants (SN) after mRNA transfection of BHK cells. Equal amounts of three replicates were pooled and loaded on denaturing SDS–PAGE. Staining for β‐actin was used as loading control.Quantification of VNA levels by antigen‐specific ELISA of supernatants from transfected BHK cells. Titers were determined in triplicate. Supernatants from cells transfected with an irrelevant VNA were used as mock control.mRNA design to encode heavy‐ and light‐chain molecules.Western blot analysis showing expression of heavy and light chains in cell lysates and accumulation in supernatants after mRNA transfection of BHK cells. Equal amounts of three replicates were pooled and loaded on denaturing SDS–PAGE. Signals correspond to heavy chain (HC), light chain (LC) and, as loading control, tubulin.Quantification of mAb levels in supernatants of BHK cells by IgG‐specific ELISA. Titers were determined in triplicate.Data information: For mock transfection, an mRNA encoding eGFP was used. UTR, untranslated region; SP, signal peptide; A(n), poly(A)‐tail. Results in (C and F) are expressed as means ± SD.Source data are available online for this figure.
Figure 1 In vitro expression of mRNA‐encoded antibodies mRNA design to encode heavy‐chain‐only VH domain (VHH)‐based neutralizing agents (VNAs). VNAs were supplemented by affinity E‐tags (Tag) and an albumin‐binding peptide (ABP).Western blot analysis of VNA‐BoNTA expression in cell lysates and supernatants (SN) after mRNA transfection of BHK cells. Equal amounts of three replicates were pooled and loaded on denaturing SDS–PAGE. Staining for β‐actin was used as loading control.Quantification of VNA levels by antigen‐specific ELISA of supernatants from transfected BHK cells. Titers were determined in triplicate. Supernatants from cells transfected with an irrelevant VNA were used as mock control.mRNA design to encode heavy‐ and light‐chain molecules.Western blot analysis showing expression of heavy and light chains in cell lysates and accumulation in supernatants after mRNA transfection of BHK cells. Equal amounts of three replicates were pooled and loaded on denaturing SDS–PAGE. Signals correspond to heavy chain (HC), light chain (LC) and, as loading control, tubulin.Quantification of mAb levels in supernatants of BHK cells by IgG‐specific ELISA. Titers were determined in triplicate.Data information: For mock transfection, an mRNA encoding eGFP was used. UTR, untranslated region; SP, signal peptide; A(n), poly(A)‐tail. Results in (C and F) are expressed as means ± SD.Source data are available online for this figure.CC BY · PubMed Central
Figure 2 Evaluation of antibody function in vitro ABoNT/A toxin was incubated either with different doses of recombinant VNA, spiked into supernatant of mock‐transfected BHK cells, or different dilutions of supernatant of BHK cells transfected with mRNA encoding VNA‐BoNTA before SNAP25 cleavage assay. In this assay, BoNT/A cleaves SNAP25 which can be inhibited by VNA binding to the toxin. Samples from cleavage assay were loaded on denaturing SDS–PAGE and BoNT/A‐mediated cleavage of endogenous SNAP25 was analyzed.BCell‐based toxicity assay to demonstrate the function of RNA‐encoded VNA‐Stx2. Supernatants from BHK cells transfected with VNA‐encoding mRNA were analyzed in a dilutions series (11 nM initial concentration). Serial dilutions of supernatants from mock‐transfected cells served as negative control. Recombinant VNA‐Stx2 was spiked into mock‐transfected medium at an initial concentration of 10 nM.C, DBinding of mRNA‐encoded anti‐rabies mAb (C) or anti‐influenza B mAb (D) expressed in BHK cell supernatants to antigen‐positive or antigen‐negative HeLa cells. Depicted is the median of phycoerythrin (PE) fluorescence of all living cells. Fluorescence was measured in triplicate. For mock transfections, supernatants of eGFP‐mRNA transfected cells were used.EBinding of mRNA‐encoded rituximab expressed in BHK cells to Raji cells. Depicted is the median of phycoerythrin (PE) fluorescence of all living cells. Fluorescence was measured in triplicate. For mock transfections, supernatants of eGFP‐mRNA transfected cells were used.FSupernatants of BHK cells transfected with mRNA encoding VRC01 or untransfected BHK cells were subjected to a Magi R5‐Tropic Antiviral Assay. Depicted are the mAb concentrations that produced either 50% (IC50) or 90% inhibition (IC90) of virus entry. Recombinant VRC01 mAb or TAK779 inhibitor was used as positive controls. Individual inhibition curves are shown in Appendix Fig S5.Data information: Results in (C, D and E) are expressed as median ± SD.
Figure 2 Evaluation of antibody function in vitro ABoNT/A toxin was incubated either with different doses of recombinant VNA, spiked into supernatant of mock‐transfected BHK cells, or different dilutions of supernatant of BHK cells transfected with mRNA encoding VNA‐BoNTA before SNAP25 cleavage assay. In this assay, BoNT/A cleaves SNAP25 which can be inhibited by VNA binding to the toxin. Samples from cleavage assay were loaded on denaturing SDS–PAGE and BoNT/A‐mediated cleavage of endogenous SNAP25 was analyzed.BCell‐based toxicity assay to demonstrate the function of RNA‐encoded VNA‐Stx2. Supernatants from BHK cells transfected with VNA‐encoding mRNA were analyzed in a dilutions series (11 nM initial concentration). Serial dilutions of supernatants from mock‐transfected cells served as negative control. Recombinant VNA‐Stx2 was spiked into mock‐transfected medium at an initial concentration of 10 nM.C, DBinding of mRNA‐encoded anti‐rabies mAb (C) or anti‐influenza B mAb (D) expressed in BHK cell supernatants to antigen‐positive or antigen‐negative HeLa cells. Depicted is the median of phycoerythrin (PE) fluorescence of all living cells. Fluorescence was measured in triplicate. For mock transfections, supernatants of eGFP‐mRNA transfected cells were used.EBinding of mRNA‐encoded rituximab expressed in BHK cells to Raji cells. Depicted is the median of phycoerythrin (PE) fluorescence of all living cells. Fluorescence was measured in triplicate. For mock transfections, supernatants of eGFP‐mRNA transfected cells were used.FSupernatants of BHK cells transfected with mRNA encoding VRC01 or untransfected BHK cells were subjected to a Magi R5‐Tropic Antiviral Assay. Depicted are the mAb concentrations that produced either 50% (IC50) or 90% inhibition (IC90) of virus entry. Recombinant VRC01 mAb or TAK779 inhibitor was used as positive controls. Individual inhibition curves are shown in Appendix Fig S5.Data information: Results in (C, D and E) are expressed as median ± SD.CC BY · PubMed Central
Figure 3 In vivo expression characteristics of antibody‐encoding mRNA Quantification of mAb titers in mice by IgG‐specific ELISA of sera obtained 24 h after a single intravenous injection of increasing amounts of mRNA‐LNP encoding anti‐rabies mAb. Each group consisted of five animals.Same sera as in (A) were subjected to a fluorescent antibody virus neutralization (FAVN) assay to determine anti‐rabies virus neutralizing titers (VNTs in international units).Quantification of mAb titers by IgG‐specific ELISA at various times after a single intravenous injection of 40 μg of mRNA‐LNP encoding anti‐rabies mAb. Five cohorts of eight mice each were alternately bled to enable the given sampling schedule.Quantification of anti‐rabies and anti‐influenza B mAb titers by IgG‐specific ELISA 1 or 24 days post‐injection of 40 μg mRNA‐LNP. Each group comprised 12 mice.Quantification of VNA‐BoNTA titers by antigen‐specific ELISA of sera at various times after a single injection of 40 μg of mRNA‐LNP encoding VNA‐BoNTA. For each sampling, a separate cohort of mice, each comprising five animals, was used.Data information: Individual measurements as well as means are given for each dose and time, respectively.
Figure 3 In vivo expression characteristics of antibody‐encoding mRNA Quantification of mAb titers in mice by IgG‐specific ELISA of sera obtained 24 h after a single intravenous injection of increasing amounts of mRNA‐LNP encoding anti‐rabies mAb. Each group consisted of five animals.Same sera as in (A) were subjected to a fluorescent antibody virus neutralization (FAVN) assay to determine anti‐rabies virus neutralizing titers (VNTs in international units).Quantification of mAb titers by IgG‐specific ELISA at various times after a single intravenous injection of 40 μg of mRNA‐LNP encoding anti‐rabies mAb. Five cohorts of eight mice each were alternately bled to enable the given sampling schedule.Quantification of anti‐rabies and anti‐influenza B mAb titers by IgG‐specific ELISA 1 or 24 days post‐injection of 40 μg mRNA‐LNP. Each group comprised 12 mice.Quantification of VNA‐BoNTA titers by antigen‐specific ELISA of sera at various times after a single injection of 40 μg of mRNA‐LNP encoding VNA‐BoNTA. For each sampling, a separate cohort of mice, each comprising five animals, was used.Data information: Individual measurements as well as means are given for each dose and time, respectively.CC BY · PubMed Central
Figure 4 mRNA‐encoded mAbs provide both prophylactic and therapeutic protection against viral or toxin challenges Schedule of prophylactic treatment before rabies challenge. Mice received a single intravenous (i.v.) injection of 40 μg of mRNA‐LNP either encoding anti‐rabies or anti‐influenza B mAbs 1 day before a lethal 5 × LD50 intramuscular (i.m.) rabies challenge. Body weight, clinical score (for both see Appendix Table S2), and survival were monitored for up to 21 days.Survival curve of mice that were treated according to the schedule in (A). A total of six mice per group were challenged.Schedule of therapeutic treatment after rabies challenge. Mice received a single intravenous injection of 40 μg of mRNA‐LNP either encoding anti‐rabies or anti‐influenza B mAbs 2 h after a lethal 5 × LD50 intramuscular rabies challenge. Body weight, clinical score (for both see Appendix Tables S3 and S4), and survival were monitored for up to 21 days.Survival curve of mice treated according to the schedule in (C). A total of six mice per group were challenged.Survival curve of mice that were treated according to schedule (C) but received different doses of mRNA‐LNP as well as buffer as further control. A total of eight mice per group were challenged.Schedule of therapeutic BoNT/A challenge. Mice received a single intravenous injection of 2 μg of recombinant VNA‐BoNTA or 40 μg of mRNA‐LNP either encoding VNA‐BoNTA or VNA‐Stx2 6 h after a lethal 4 × LD50 intravenous BoNT/A challenge. Survival was monitored for up to 6 days.Survival curve of mice that were treated according to the schedule in (F). A total of ten mice per group were challenged.
Figure 4 mRNA‐encoded mAbs provide both prophylactic and therapeutic protection against viral or toxin challenges Schedule of prophylactic treatment before rabies challenge. Mice received a single intravenous (i.v.) injection of 40 μg of mRNA‐LNP either encoding anti‐rabies or anti‐influenza B mAbs 1 day before a lethal 5 × LD50 intramuscular (i.m.) rabies challenge. Body weight, clinical score (for both see Appendix Table S2), and survival were monitored for up to 21 days.Survival curve of mice that were treated according to the schedule in (A). A total of six mice per group were challenged.Schedule of therapeutic treatment after rabies challenge. Mice received a single intravenous injection of 40 μg of mRNA‐LNP either encoding anti‐rabies or anti‐influenza B mAbs 2 h after a lethal 5 × LD50 intramuscular rabies challenge. Body weight, clinical score (for both see Appendix Tables S3 and S4), and survival were monitored for up to 21 days.Survival curve of mice treated according to the schedule in (C). A total of six mice per group were challenged.Survival curve of mice that were treated according to schedule (C) but received different doses of mRNA‐LNP as well as buffer as further control. A total of eight mice per group were challenged.Schedule of therapeutic BoNT/A challenge. Mice received a single intravenous injection of 2 μg of recombinant VNA‐BoNTA or 40 μg of mRNA‐LNP either encoding VNA‐BoNTA or VNA‐Stx2 6 h after a lethal 4 × LD50 intravenous BoNT/A challenge. Survival was monitored for up to 6 days.Survival curve of mice that were treated according to the schedule in (F). A total of ten mice per group were challenged.CC BY · PubMed Central
Figure 5 mRNA‐encoded mAb protects mice from lethal tumor challenge Schedule of tumor challenge and mRNA treatments. On Day 0, mice received an intravenous (i.v.) administration of 2 × 106 Raji Luc cells. At the indicated times (lower arrows), mice received intravenous injections of either 10 or 50 μg of mRNA‐LNP encoding rituximab. Survival and tumor development were monitored for up to 28 days.Tumor development was assessed by whole‐body luminescence imaging at the indicated times after tumor challenge. Each group comprised 12 mice.Survival of mice treated according to the schedule in (A). Each group comprised 12 mice.Representative luminescence images of mice either treated with two different doses of mRNA‐LNP encoding rituximab or untreated mice at day 13 after tumor challenge.Schedule of tumor challenge and mRNA treatments. On Day 0, mice received an intravenous (i.v.) administration of 2 × 106 Raji Luc cells. At the indicated times (lower arrows), mice received intravenous injections of 50 μg of mRNA‐LNP encoding rituximab or control antibody or 200 μg of recombinant rituximab. Survival and tumor development were monitored for up to 24 days.Tumor development of experiment as in (E) was assessed by whole‐body luminescence imaging at the indicated times after tumor challenge. Each group comprised 12 mice.Data information: Results in (B and F) are expressed as means ± SD.
Figure 5 mRNA‐encoded mAb protects mice from lethal tumor challenge Schedule of tumor challenge and mRNA treatments. On Day 0, mice received an intravenous (i.v.) administration of 2 × 106 Raji Luc cells. At the indicated times (lower arrows), mice received intravenous injections of either 10 or 50 μg of mRNA‐LNP encoding rituximab. Survival and tumor development were monitored for up to 28 days.Tumor development was assessed by whole‐body luminescence imaging at the indicated times after tumor challenge. Each group comprised 12 mice.Survival of mice treated according to the schedule in (A). Each group comprised 12 mice.Representative luminescence images of mice either treated with two different doses of mRNA‐LNP encoding rituximab or untreated mice at day 13 after tumor challenge.Schedule of tumor challenge and mRNA treatments. On Day 0, mice received an intravenous (i.v.) administration of 2 × 106 Raji Luc cells. At the indicated times (lower arrows), mice received intravenous injections of 50 μg of mRNA‐LNP encoding rituximab or control antibody or 200 μg of recombinant rituximab. Survival and tumor development were monitored for up to 24 days.Tumor development of experiment as in (E) was assessed by whole‐body luminescence imaging at the indicated times after tumor challenge. Each group comprised 12 mice.Data information: Results in (B and F) are expressed as means ± SD.CC BY · PubMed Central

Verification

Claims the paper makes

63 Own result · 37 Own interpretation · 13 Supported · 13 Own method · 8 Partly supported · 8 No full text of the sources · 8 No basis given · 2 Sources not found · 1 Not checked yet · accuracy not yet measured

  • It may state two separate claims as one. 28
  • Probably not a substantial claim. 23
49 of 49

  • The paper relies on this without support.

    Passive immunization confers only a relatively short duration of protection compared to vaccines.

    “Moreover, passive immunization confers only a relatively short duration of protection compared to vaccines.”

  • The paper relies on this without support.

    DNA-based passive immunization suffers from the risk of genomic integration, potentially causing fatal mutations.

    “In general, however, DNA‐based passive immunization suffers from the risk of genomic integration, potentially causing fatal mutations.”

  • The paper relies on this without support.

    Immunogenicity of virus particles is a main obstacle for the use of viral vectors for DNA-mediated passive immunization.

    “In addition, immunogenicity of virus particles has to be considered a main obstacle for the use of this type of vectors for DNA‐mediated passive immunization.”

  • The paper relies on this without support.

    Efficacious treatment with therapeutic proteins depends on both timely delivery and achieving protective levels.

    “Efficacious treatment with therapeutic proteins depends on both timely delivery and achieving protective levels.”

  • The paper relies on this without support.

    The time window for efficacious rabies treatment is limited by the time it takes until the virus reaches the brain.

    “The time window for an efficacious treatment is limited by the time it takes until the virus finally reaches the brain.”

  • The paper relies on this without support.

    In mice, rabies infection proceeds rapidly.

    “In mice, rabies infection is believed to proceed rapidly.”

  • The paper relies on this without support.

    The intramuscular route resembles the most common route of rabies infection.

    “Since this route resembles the most common route of rabies infection, IM challenge was used throughout the present study.”

  • The paper relies on this without support.

    Therapeutic doses of today's recombinant antibodies are often quite high.

    “However, therapeutic doses of today's recombinant antibodies are often quite high.”

  • The paper relies on this without support.

    In vivo, many anti-rabies antibodies become ineffective after the virus has entered the CNS.

    “In vivo, many anti‐rabies antibodies become ineffective after the virus has entered the CNS.”

  • The paper relies on this without support.

    The time window for efficacious antibody intervention has not been defined for mice for which a very fast progress of the disease has been reported.

    “Furthermore, the time window for efficacious antibody intervention has not been defined for mice for which a very fast progress of the disease has been reported.”

  • The paper relies on this without support.

    Any protein therapy has the inherent risk of inducing an anti-drug antibody (ADA) response which may limit drug efficacy, particularly over time.

    “Any protein therapy has the inherent risk of inducing an anti‐drug antibody (ADA) response which may limit drug efficacy, particularly over time.”

  • The paper relies on this without support.

    The probability of an ADA response is especially high for proteins that are foreign to the body.

    “The probability of an ADA response is especially high for proteins that are foreign to the body.”

  • The paper relies on this without support.

    The risk of ADA response may be further increased if the protein is encoded by a nucleic acid which may trigger an innate immune response via diverse cellular sensors.

    “The risk may be further increased, if the protein is encoded by a nucleic acid which may trigger an innate immune response via diverse cellular sensors.”

  • The paper relies on this without support.

    Any passive vaccination platform needs to provide effective antibody levels soon after drug administration.

    “Any passive vaccination platform needs to provide effective antibody levels soon after drug administration.”

  • The paper relies on this without support.

    There are only three approved monoclonal antibodies against infectious diseases today.

    “there are only three approved monoclonal antibodies against infectious diseases today”

  • The paper relies on this without support.

    Antibodies are at a disadvantage compared to antibiotics and vaccines, predominantly for economic reasons.

    “Thus far, antibodies are at a disadvantage compared to antibiotics and vaccines, predominantly for economic reasons.”

  • The paper relies on this without support.

    There is a strong demand for cost-effective alternatives to the administration of recombinant proteins.

    “Hence, there is a strong demand for cost‐effective alternatives to the administration of recombinant proteins.”

  • The paper relies on this without support.

    DNA-based antibody expression reaches protective serum titers in various preclinical models.

    “DNA‐based antibody expression proved to reach protective serum titers in various preclinical models.”

  • The paper relies on this without support.

    Permanent or at least long-lasting expression is often undesired for passive immunization.

    “However, permanent or at least long‐lasting expression is often undesired for passive immunization, thus requiring sophisticated approaches for the clinic.”

  • The paper relies on this without support.

    Transience is inherent to mRNA.

    “By contrast, transience is inherent to another nucleic acid, mRNA.”

  • The paper relies on this without support.

    Recent studies suggested mRNA as a means for molecular therapies requiring the delivery of functional proteins.

    “Moreover, a number of recent intriguing studies principally suggested mRNA as a means for molecular therapies requiring the delivery of functional proteins.”
21 of 21

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Metadata

Authors
Thran, M., Mukherjee, J., Pönisch, M., Fiedler, K., Thess, A., Mui, B. L., Hope, M. J., Tam, Y. K., Horscroft, N., Heidenreich, R., Fotin‐Mleczek, M., Shoemaker, C. B., & Schlake, T.
Affiliations
  • CureVac (Germany) (DE)
  • Tufts University (US)
  • Acuitas Therapeutics (Canada) (CA)
Corresponding author
Schlake, Thomas
ORCID
Venue
EMBO Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2017-08-09
Volume
9
Issue
10
Pages
1434-1447
ISSN
  • 1757-4676 (ISSN-L)
  • 1757-4684
DOI
10.15252/emmm.201707678
PMC
PMC5623855
OpenAlex
W2742522266
Cited by
166
References
56
Citations by year
2026: 9 · 2025: 19 · 2024: 30 · 2023: 24 · 2022: 25 · 2021: 25 · 2020: 20 · 2019: 8 · 2018: 6
FWCI
3.31
Type
journal article
Language
en
Open access
Licence
Locations
  • EMBO Molecular Medicine (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Keywords
mRNA vaccines, passive immunization, lipid nanoparticle delivery, rabies virus, botulinum toxin, cancer immunotherapy, therapeutic antibodies, prophylactic vaccination, antibody titers
MeSH terms
Animals, Antibodies, Viral, Botulinum Antitoxin, Botulism, Dose-Response Relationship, Immunologic, Female, Humans, Immunization, Passive, Mice, Inbred BALB C, Rabies, Rabies Vaccines, Rabies virus, RNA, Messenger, Mice, Nanoparticles, Post-Exposure Prophylaxis

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