Radioprotection of healthy tissue via nanoparticle-delivered mRNA encoding for a damage-suppressor protein found in tardigrades

被引：0

作者：

Kirtane, Ameya R. ^{[1
,2
]}

Bi, Jianling ^{[3
,4
,5
]}

Rajesh, Netra U. ^{[2
,6
,7
]}

Tang, Chaoyang ^{[2
]}

Jimenez, Miguel ^{[2
,8
]}

Witt, Emily ^{[3
,4
,5
]}

Mcgovern, Megan K. ^{[3
,4
,5
]}

Cafi, Arielle B. ^{[3
,4
,5
]}

Hatfield, Samual J. ^{[3
,4
,5
]}

Rosenstock, Lauren ^{[3
,4
,5
]}

Becker, Sarah L. ^{[1
,9
]}

Machado, Nicole ^{[2
,10
,11
]}

Venkatachalam, Veena ^{[12
]}

Freitas, Dylan ^{[1
]}

Huang, Xisha ^{[1
]}

Chan, Alvin ^{[1
,2
,8
]}

Lopes, Aaron ^{[1
,2
,8
]}

Kim, Hyunjoon ^{[2
,13
]}

Kim, Nayoon ^{[2
,14
]}

Collins, Joy E. ^{[1
,2
]}

Howard, Michelle E. ^{[3
,15
]}

Manchkanti, Srija ^{[16
]}

Hong, Theodore S. ^{[17
]}

Byrne, James D. ^{[3
,4
,5
,15
]}

Traverso, Giovanni ^{[1
,2
,8
,18
]}

机构：

[1] Harvard Med Sch, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA

[2] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[3] Univ Iowa, Dept Radiat Oncol, Iowa City, IA 52242 USA

[4] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA

[5] Univ Iowa, Holden Comprehens Canc Ctr, Iowa City, IA 52246 USA

[6] Stanford Univ, Dept Bioengn, Stanford, CA USA

[7] Univ Toronto, Fac Appl Sci & Engn, Toronto, ON, Canada

[8] MIT, Dept Mech Engn, Cambridge, MA 02139 USA

[9] Oregon Hlth & Sci Univ, Sch Med, Portland, OR USA

[10] Univ Toronto, Fac Arts & Sci, Toronto, ON, Canada

[11] Univ Oxford, Dept Psychiat, Oxford, England

[12] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA

[13] Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS USA

[14] Univ Washington, Sch Med, Seattle, WA USA

[15] Univ Iowa, Holden Comprehens Canc Ctr, Dept Radiat Oncol, Free Rad & Radiat Biol Program, Iowa City, IA 52242 USA

[16] Univ Iowa, Carver Coll Med, Iowa City, IA USA

[17] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA

[18] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

来源：

NATURE BIOMEDICAL ENGINEERING | 2025年

关键词：

LIPID NANOPARTICLES; RADIATION-THERAPY; SIRNA DELIVERY; PROTON SPONGE; ADVANCED HEAD; PHASE-III; IN-VIVO; OUTCOMES; RISK; CHEMORADIOTHERAPY;

D O I：

10.1038/s41551-025-01360-5

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Patients undergoing radiation therapy experience debilitating side effects because of toxicity arising from radiation-induced DNA strand breaks in normal peritumoural cells. Here, inspired by the ability of tardigrades to resist extreme radiation through the expression of a damage-suppressor protein that binds to DNA and reduces strand breaks, we show that the local and transient expression of the protein can reduce radiation-induced DNA damage in oral and rectal epithelial tissues (which are commonly affected during radiotherapy for head-and-neck and prostate cancers, respectively). We used ionizable lipid nanoparticles supplemented with biodegradable cationic polymers to enhance the transfection efficiency and delivery of messenger RNA encoding the damage-suppressor protein into buccal and rectal tissues. In mice with orthotopic oral cancer, messenger RNA-based radioprotection of normal tissue preserved the efficacy of radiation therapy. The strategy may be broadly applicable to the protection of healthy tissue from DNA-damaging agents.

引用

页数：22