Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors

Yasmin Granot-Matok; Assaf Ezra; Srinivas Ramishetti; Preeti Sharma; Gonna Somu Naidu; Itai Benhar; Dan Peer

doi:10.7150/thno.82228

Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors

Yasmin Granot-Matok, Assaf Ezra, Srinivas Ramishetti, Preeti Sharma, Gonna Somu Naidu, Itai Benhar, Dan Peer

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Background and rationale: Cancer therapy have evolved remarkably over the past decade, providing new strategies to inhibit cancer cell growth using immune modulation, with or without gene therapy. Specifically, suicide gene therapies and immunotoxins have been investigated for the treatment of tumors by direct cancer cell cytotoxicity. Recent advances in mRNA delivery also demonstrated the potential of mRNA-based vaccines and immune-modulators for cancer therapeutics by utilizing nanocarriers for mRNA delivery. Methods: We designed a bacterial toxin-encoding modified mRNA, delivered by lipid nanoparticles into a B16-melanoma mouse model. Results: We showed that local administration of LNPs entrapping a modified mRNA that encodes for a bacterial toxin, induced significant anti-tumor effects and improved overall survival of treated mice. Conclusions: We propose mmRNA-loaded LNPs as a new class of anti-tumoral, toxin-based therapy.

Original language	English (US)
Pages (from-to)	3497-3508
Number of pages	12
Journal	Theranostics
Volume	13
Issue number	11
DOIs	https://doi.org/10.7150/thno.82228
State	Published - 2023

Keywords

cancer therapy
gene therapy
immunotoxins
lipid nanoparticles
mRNA
suicide-gene therapy
Genetic Therapy
RNA, Messenger/genetics
Nanoparticles
Animals
Neoplasms/therapy
Bacterial Toxins/genetics
Mice
Liposomes

ASJC Scopus subject areas

Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Medicine (miscellaneous)

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10.7150/thno.82228

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title = "Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors",

abstract = "Background and rationale: Cancer therapy have evolved remarkably over the past decade, providing new strategies to inhibit cancer cell growth using immune modulation, with or without gene therapy. Specifically, suicide gene therapies and immunotoxins have been investigated for the treatment of tumors by direct cancer cell cytotoxicity. Recent advances in mRNA delivery also demonstrated the potential of mRNA-based vaccines and immune-modulators for cancer therapeutics by utilizing nanocarriers for mRNA delivery. Methods: We designed a bacterial toxin-encoding modified mRNA, delivered by lipid nanoparticles into a B16-melanoma mouse model. Results: We showed that local administration of LNPs entrapping a modified mRNA that encodes for a bacterial toxin, induced significant anti-tumor effects and improved overall survival of treated mice. Conclusions: We propose mmRNA-loaded LNPs as a new class of anti-tumoral, toxin-based therapy.",

keywords = "cancer therapy, gene therapy, immunotoxins, lipid nanoparticles, mRNA, suicide-gene therapy, Genetic Therapy, RNA, Messenger/genetics, Nanoparticles, Animals, Neoplasms/therapy, Bacterial Toxins/genetics, Mice, Liposomes",

author = "Yasmin Granot-Matok and Assaf Ezra and Srinivas Ramishetti and Preeti Sharma and Naidu, {Gonna Somu} and Itai Benhar and Dan Peer",

note = "Funding Information: This work was supported in part by the Shmunis Family Foundation awarded to D.P. Publisher Copyright: {\textcopyright} The author(s).",

year = "2023",

doi = "10.7150/thno.82228",

language = "English (US)",

volume = "13",

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T1 - Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors

AU - Granot-Matok, Yasmin

AU - Ezra, Assaf

AU - Ramishetti, Srinivas

AU - Sharma, Preeti

AU - Naidu, Gonna Somu

AU - Benhar, Itai

AU - Peer, Dan

N1 - Funding Information: This work was supported in part by the Shmunis Family Foundation awarded to D.P. Publisher Copyright: © The author(s).

PY - 2023

Y1 - 2023

N2 - Background and rationale: Cancer therapy have evolved remarkably over the past decade, providing new strategies to inhibit cancer cell growth using immune modulation, with or without gene therapy. Specifically, suicide gene therapies and immunotoxins have been investigated for the treatment of tumors by direct cancer cell cytotoxicity. Recent advances in mRNA delivery also demonstrated the potential of mRNA-based vaccines and immune-modulators for cancer therapeutics by utilizing nanocarriers for mRNA delivery. Methods: We designed a bacterial toxin-encoding modified mRNA, delivered by lipid nanoparticles into a B16-melanoma mouse model. Results: We showed that local administration of LNPs entrapping a modified mRNA that encodes for a bacterial toxin, induced significant anti-tumor effects and improved overall survival of treated mice. Conclusions: We propose mmRNA-loaded LNPs as a new class of anti-tumoral, toxin-based therapy.

AB - Background and rationale: Cancer therapy have evolved remarkably over the past decade, providing new strategies to inhibit cancer cell growth using immune modulation, with or without gene therapy. Specifically, suicide gene therapies and immunotoxins have been investigated for the treatment of tumors by direct cancer cell cytotoxicity. Recent advances in mRNA delivery also demonstrated the potential of mRNA-based vaccines and immune-modulators for cancer therapeutics by utilizing nanocarriers for mRNA delivery. Methods: We designed a bacterial toxin-encoding modified mRNA, delivered by lipid nanoparticles into a B16-melanoma mouse model. Results: We showed that local administration of LNPs entrapping a modified mRNA that encodes for a bacterial toxin, induced significant anti-tumor effects and improved overall survival of treated mice. Conclusions: We propose mmRNA-loaded LNPs as a new class of anti-tumoral, toxin-based therapy.

KW - cancer therapy

KW - gene therapy

KW - immunotoxins

KW - lipid nanoparticles

KW - mRNA

KW - suicide-gene therapy

KW - Genetic Therapy

KW - RNA, Messenger/genetics

KW - Nanoparticles

KW - Animals

KW - Neoplasms/therapy

KW - Bacterial Toxins/genetics

KW - Mice

KW - Liposomes

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ER -

Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors

Abstract

Keywords

ASJC Scopus subject areas

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