Recent advances in nanoparticulate RNA delivery systems
Nanoparticle-based RNA delivery has shown great progress in recent years with the approval of two mRNA vaccines for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and a liver-targeted siRNA therapy. Here, we discuss the preclinical and clinical advancement of new generations of RNA delivery therapies along multiple axes. Improvements in cargo design such as RNA circularization and data-driven untranslated region optimization can drive better mRNA expression. New materials discovery research has driven improved delivery to extrahepatic targets such as the lung and splenic immune cells, which could lead to pulmonary gene therapy and better cancer vaccines, respectively. Other organs and even specific cell types can be targeted for delivery via conjugation of small molecule ligands, antibodies, or peptides to RNA delivery nanoparticles. Moreover, the immune response to any RNA delivery nanoparticle plays a crucial role in determining efficacy. Targeting increased immunogenicity without induction of reactogenic side effects is crucial for vaccines, while minimization of immune response is important for gene therapies. New developments have addressed each of these priorities. Last, we discuss the range of RNA delivery clinical trials targeting diverse organs, cell types, and diseases and suggest some key advances that may play a role in the next wave of therapies.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:121 |
|---|---|
| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 121(2024), 11 vom: 12. März, Seite e2307798120 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Witten, Jacob [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antibodies |
|---|
| Anmerkungen: |
Date Completed 06.03.2024 Date Revised 20.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1073/pnas.2307798120 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369274318 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369274318 | ||
| 003 | DE-627 | ||
| 005 | 20240320234520.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240305s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1073/pnas.2307798120 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1337.xml |
| 035 | |a (DE-627)NLM369274318 | ||
| 035 | |a (NLM)38437569 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Witten, Jacob |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Recent advances in nanoparticulate RNA delivery systems |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.03.2024 | ||
| 500 | |a Date Revised 20.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Nanoparticle-based RNA delivery has shown great progress in recent years with the approval of two mRNA vaccines for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and a liver-targeted siRNA therapy. Here, we discuss the preclinical and clinical advancement of new generations of RNA delivery therapies along multiple axes. Improvements in cargo design such as RNA circularization and data-driven untranslated region optimization can drive better mRNA expression. New materials discovery research has driven improved delivery to extrahepatic targets such as the lung and splenic immune cells, which could lead to pulmonary gene therapy and better cancer vaccines, respectively. Other organs and even specific cell types can be targeted for delivery via conjugation of small molecule ligands, antibodies, or peptides to RNA delivery nanoparticles. Moreover, the immune response to any RNA delivery nanoparticle plays a crucial role in determining efficacy. Targeting increased immunogenicity without induction of reactogenic side effects is crucial for vaccines, while minimization of immune response is important for gene therapies. New developments have addressed each of these priorities. Last, we discuss the range of RNA delivery clinical trials targeting diverse organs, cell types, and diseases and suggest some key advances that may play a role in the next wave of therapies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
| 650 | 7 | |a Antibodies |2 NLM | |
| 650 | 7 | |a Cancer Vaccines |2 NLM | |
| 700 | 1 | |a Hu, Yizong |e verfasserin |4 aut | |
| 700 | 1 | |a Langer, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Daniel G |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Proceedings of the National Academy of Sciences of the United States of America |d 1915 |g 121(2024), 11 vom: 12. März, Seite e2307798120 |w (DE-627)NLM000008982 |x 1091-6490 |7 nnns |
| 773 | 1 | 8 | |g volume:121 |g year:2024 |g number:11 |g day:12 |g month:03 |g pages:e2307798120 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1073/pnas.2307798120 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 121 |j 2024 |e 11 |b 12 |c 03 |h e2307798120 | ||