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Article ; Online: mRNA-based therapeutics: looking beyond COVID-19 vaccines.

Parhiz, Hamideh / Atochina-Vasserman, Elena N / Weissman, Drew

2024 Volume 403, Issue 10432, Page(s) 1192–1204

Abstract: Recent advances in mRNA technology and its delivery have enabled mRNA-based therapeutics to enter a new era in medicine. The rapid, potent, and transient nature of mRNA-encoded proteins, without the need to enter the nucleus or the risk of genomic ... ...

Abstract	Recent advances in mRNA technology and its delivery have enabled mRNA-based therapeutics to enter a new era in medicine. The rapid, potent, and transient nature of mRNA-encoded proteins, without the need to enter the nucleus or the risk of genomic integration, makes them desirable tools for treatment of a range of diseases, from infectious diseases to cancer and monogenic disorders. The rapid pace and ease of mass-scale manufacturability of mRNA-based therapeutics supported the global response to the COVID-19 pandemic. Nonetheless, challenges remain with regards to mRNA stability, duration of expression, delivery efficiency, and targetability, to broaden the applicability of mRNA therapeutics beyond COVID-19 vaccines. By learning from the rapidly expanding preclinical and clinical studies, we can optimise the mRNA platform to meet the clinical needs of each disease. Here, we will summarise the recent advances in mRNA technology; its use in vaccines, immunotherapeutics, protein replacement therapy, and genomic editing; and its delivery to desired specific cell types and organs for development of a new generation of targeted mRNA-based therapeutics.
MeSH term(s)	Humans ; COVID-19 Vaccines ; COVID-19/prevention & control ; Pandemics ; Medicine ; RNA, Messenger/therapeutic use
Chemical Substances	COVID-19 Vaccines ; RNA, Messenger
Language	English
Publishing date	2024-03-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(23)02444-3
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Article ; Online: Debunking mRNA Vaccine Misconceptions-An Overview for Medical Professionals.

Hitti, Frederick L / Weissman, Drew

The American journal of medicine

2021 Volume 134, Issue 6, Page(s) 703–704

MeSH term(s)	COVID-19/genetics ; COVID-19/prevention & control ; Health Personnel/education ; Health Personnel/trends ; Humans ; Therapeutic Misconception ; Vaccines, Synthetic/adverse effects ; Vaccines, Synthetic/pharmacology ; Vaccines, Synthetic/therapeutic use ; COVID-19 Drug Treatment ; mRNA Vaccines
Chemical Substances	Vaccines, Synthetic
Language	English
Publishing date	2021-03-15
Publishing country	United States
Document type	Editorial
ZDB-ID	80015-6
ISSN	1555-7162 ; 1873-2178 ; 0002-9343 ; 1548-2766
ISSN (online)	1555-7162 ; 1873-2178
ISSN	0002-9343 ; 1548-2766
DOI	10.1016/j.amjmed.2021.02.004
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Article ; Online: Emerging strategies for nanomedicine in autoimmunity.

Thatte, Ajay S / Billingsley, Margaret M / Weissman, Drew / Melamed, Jilian R / Mitchell, Michael J

Advanced drug delivery reviews

2024 Volume 207, Page(s) 115194

Abstract: Autoimmune disorders have risen to be among the most prevalent chronic diseases across the globe, affecting approximately 5-7% of the population. As autoimmune diseases steadily rise in prevalence, so do the number of potential therapeutic strategies to ... ...

Abstract	Autoimmune disorders have risen to be among the most prevalent chronic diseases across the globe, affecting approximately 5-7% of the population. As autoimmune diseases steadily rise in prevalence, so do the number of potential therapeutic strategies to combat them. In recent years, fundamental research investigating autoimmune pathologies has led to the emergence of several cellular targets that provide new therapeutic opportunities. However, key challenges persist in terms of accessing and specifically combating the dysregulated, self-reactive cells while avoiding systemic immune suppression and other off-target effects. Fortunately, the continued advancement of nanomedicines may provide strategies to address these challenges and bring innovative autoimmunity therapies to the clinic. Through precise engineering and rational design, nanomedicines can possess a variety of physicochemical properties, surface modifications, and cargoes, allowing for specific targeting of therapeutics to pathological cell and organ types. These advances in nanomedicine have been demonstrated in cancer therapies and have the broad potential to advance applications in autoimmunity therapies as well. In this review, we focus on leveraging the power of nanomedicine for prevalent autoimmune disorders throughout the body. We expand on three key areas for the development of autoimmunity therapies - avoiding systemic immunosuppression, balancing interactions with the immune system, and elevating current platforms for delivering complex cargoes - and emphasize how nanomedicine-based strategies can overcome these barriers and enable the development of next-generation, clinically relevant autoimmunity therapies.
MeSH term(s)	Humans ; Nanomedicine ; Autoimmunity ; Autoimmune Diseases/drug therapy ; Immune System/pathology ; Immunosuppression Therapy ; Neoplasms/drug therapy ; Neoplasms/pathology
Language	English
Publishing date	2024-02-10
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2024.115194
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Article ; Online: Author Correction: mRNA vaccines for infectious diseases: principles, delivery and clinical translation.

Chaudhary, Namit / Weissman, Drew / Whitehead, Kathryn A

Nature reviews. Drug discovery

2021 Volume 20, Issue 11, Page(s) 880

Language	English
Publishing date	2021-09-20
Publishing country	England
Document type	Published Erratum
ZDB-ID	2062954-0
ISSN	1474-1784 ; 1474-1776
ISSN (online)	1474-1784
ISSN	1474-1776
DOI	10.1038/s41573-021-00321-2
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Zs.A 5564: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Development of vaccines and antivirals for combating viral pandemics.

Pardi, Norbert / Weissman, Drew

Nature biomedical engineering

2020 Volume 4, Issue 12, Page(s) 1128–1133

MeSH term(s)	Adenoviridae/genetics ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19/virology ; Genetic Vectors/genetics ; Genetic Vectors/immunology ; Genetic Vectors/metabolism ; Humans ; Pandemics ; RNA, Messenger/genetics ; RNA, Messenger/immunology ; RNA, Messenger/metabolism ; SARS-CoV-2/isolation & purification ; Viral Vaccines/immunology
Chemical Substances	Antiviral Agents ; RNA, Messenger ; Viral Vaccines
Language	English
Publishing date	2020-11-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2157-846X
ISSN (online)	2157-846X
DOI	10.1038/s41551-020-00658-w
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Article ; Online: mRNA transcript therapy.

Weissman, Drew

Expert review of vaccines

2015 Volume 14, Issue 2, Page(s) 265–281

Abstract: mRNA is the central molecule of all forms of life. It is generally accepted that current life on Earth descended from an RNA world. mRNA, after its first therapeutic description in 1992, has recently come into increased focus as a method to deliver ... ...

Abstract	mRNA is the central molecule of all forms of life. It is generally accepted that current life on Earth descended from an RNA world. mRNA, after its first therapeutic description in 1992, has recently come into increased focus as a method to deliver genetic information. The recent solution to the two main difficulties in using mRNA as a therapeutic, immune stimulation and potency, has provided the basis for a wide range of applications. While mRNA-based cancer immunotherapies have been in clinical trials for a few years, novel approaches; including, in vivo delivery of mRNA to replace or supplement proteins, mRNA-based generation of pluripotent stem cells, or genome engineering using mRNA-encoded meganucleases are beginning to be realized. This review presents the current state of mRNA drug technologies and potential applications, as well as discussing the challenges and prospects in mRNA development and drug discovery.
MeSH term(s)	Drug Delivery Systems ; Drug Design ; Drug Discovery ; Genetic Therapy ; Humans ; Immunotherapy ; Pluripotent Stem Cells/metabolism ; Proteins/metabolism ; Pseudouridine ; RNA Stability ; RNA, Messenger/administration & dosage ; RNA, Messenger/genetics ; RNA, Messenger/immunology ; Technology, Pharmaceutical ; Vaccines, DNA/administration & dosage ; Vaccines, DNA/genetics ; Vaccines, DNA/immunology
Chemical Substances	Proteins ; RNA, Messenger ; Vaccines, DNA ; Pseudouridine (1445-07-4)
Keywords	covid19
Language	English
Publishing date	2015-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2181284-6
ISSN	1744-8395 ; 1476-0584
ISSN (online)	1744-8395
ISSN	1476-0584
DOI	10.1586/14760584.2015.973859
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Article ; Online: Hepatitis C virus modified sE2

Haga, Yuki / Meyer, Keith / Sung, Molly M H / Reagan, Erin K / Weissman, Drew / Ray, Ranjit

Journal of virology

2023 Volume 98, Issue 1, Page(s) e0180923

Abstract: The rational selection of hepatitis C virus (HCV) vaccine antigen will aid in the prevention of future chronic liver disease burden and associated healthcare costs. We have previously shown that HCV E2 glycoprotein is not highly immunogenic, and the ... ...

Abstract	The rational selection of hepatitis C virus (HCV) vaccine antigen will aid in the prevention of future chronic liver disease burden and associated healthcare costs. We have previously shown that HCV E2 glycoprotein is not highly immunogenic, and the modification of E2 reduced CD81 binding and displayed altered cytokine and protective immune responses
MeSH term(s)	Animals ; Humans ; Mice ; Hepacivirus/genetics ; Hepatitis C ; Hepatitis C Antibodies ; Hepatitis C Antigens ; Leukocytes, Mononuclear ; RNA, Messenger ; Viral Envelope Proteins/metabolism ; Viral Hepatitis Vaccines ; Viral Vaccines
Chemical Substances	Hepatitis C Antibodies ; Hepatitis C Antigens ; RNA, Messenger ; Viral Envelope Proteins ; Viral Hepatitis Vaccines ; Viral Vaccines
Language	English
Publishing date	2023-12-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01809-23
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Article ; Online: Hepatitis C virus E1 and modified E2 delivered from an mRNA vaccine induces protective immunity.

Patra, Tapas / Meyer, Keith / Haga, Yuki / Reagan, Erin K / Weissman, Drew / Ray, Ranjit

NPJ vaccines

2023 Volume 8, Issue 1, Page(s) 42

Abstract: Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced ... ...

Abstract	Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. Vaccination with a mRNA-LNP expressing soluble E1 (sE1) significantly reduced vv/HCV titer in the mouse ovary. However, the addition of sE2 mRNA-LNP for immunization impaired the efficacy of the sE1 construct. Further analysis showed that Th1 related cytokine responses to the sE1 mRNA-LNP were significantly altered in the presence of sE2 following co-immunization. Evaluation of immunogenicity revealed that the use of modified sE2
Language	English
Publishing date	2023-03-18
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-023-00635-9
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Article ; Online: Progress with induction of HIV broadly neutralizing antibodies in the Duke Consortia for HIV/AIDS Vaccine Development.

Haynes, Barton F / Wiehe, Kevin / Alam, S Munir / Weissman, Drew / Saunders, Kevin O

Current opinion in HIV and AIDS

2023 Volume 18, Issue 6, Page(s) 300–308

Abstract: Purpose of review: Design of an HIV vaccine that can induce broadly neutralizing antibodies (bnAbs) is a major goal. However, HIV bnAbs are not readily made by the immune system. Rather HIV bnAbs are disfavored by a number of virus and host factors. The ...

Abstract	Purpose of review: Design of an HIV vaccine that can induce broadly neutralizing antibodies (bnAbs) is a major goal. However, HIV bnAbs are not readily made by the immune system. Rather HIV bnAbs are disfavored by a number of virus and host factors. The purpose of the review is to discuss recent progress made in the design and use of immunogens capable of inducing HIV bnAbs in the Duke Consortia for HIV/AIDS Vaccine Development. Recent findings: New immunogens capable of binding with high affinity to unmutated common ancestors (UCAs) of bnAb B cell lineages have been designed and strategies for stabilization of HIV Env in its prefusion state are being developed. Success is starting to be translated from preclinical studies of UCA-targeting immunogens in animals, to success of initiating bnAb lineages in humans. Summary: Recent progress has been made in both immunogen design and in achieving bnAb B cell lineage induction in animal models and now in human clinical trials. With continued progress, a practical HIV/AIDS vaccine may be possible. However, host constraints on full bnAb maturation remain as potential roadblocks for full maturation of some types of bnAbs.
Language	English
Publishing date	2023-09-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2502511-9
ISSN	1746-6318 ; 1746-630X
ISSN (online)	1746-6318
ISSN	1746-630X
DOI	10.1097/COH.0000000000000820
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Article ; Online: mRNA vaccines for infectious diseases: principles, delivery and clinical translation.

Chaudhary, Namit / Weissman, Drew / Whitehead, Kathryn A

Nature reviews. Drug discovery

2021 Volume 20, Issue 11, Page(s) 817–838

Abstract: Over the past several decades, messenger RNA (mRNA) vaccines have progressed from a scepticism-inducing idea to clinical reality. In 2020, the COVID-19 pandemic catalysed the most rapid vaccine development in history, with mRNA vaccines at the forefront ... ...

Abstract	Over the past several decades, messenger RNA (mRNA) vaccines have progressed from a scepticism-inducing idea to clinical reality. In 2020, the COVID-19 pandemic catalysed the most rapid vaccine development in history, with mRNA vaccines at the forefront of those efforts. Although it is now clear that mRNA vaccines can rapidly and safely protect patients from infectious disease, additional research is required to optimize mRNA design, intracellular delivery and applications beyond SARS-CoV-2 prophylaxis. In this Review, we describe the technologies that underlie mRNA vaccines, with an emphasis on lipid nanoparticles and other non-viral delivery vehicles. We also overview the pipeline of mRNA vaccines against various infectious disease pathogens and discuss key questions for the future application of this breakthrough vaccine platform.
MeSH term(s)	COVID-19/epidemiology ; COVID-19/prevention & control ; Clinical Trials as Topic ; Communicable Disease Control/methods ; Communicable Disease Control/trends ; Drug Design ; Drug Development/methods ; Humans ; RNA, Messenger/genetics ; SARS-CoV-2 ; Vaccines, Synthetic/classification ; Vaccines, Synthetic/pharmacology ; mRNA Vaccines
Chemical Substances	RNA, Messenger ; Vaccines, Synthetic
Language	English
Publishing date	2021-08-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2062954-0
ISSN	1474-1784 ; 1474-1776
ISSN (online)	1474-1784
ISSN	1474-1776
DOI	10.1038/s41573-021-00283-5
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