Development of Ultrasound-Visualized Tumor-Targeting Engineered Bacteria for Precise Tumor Therapy DOI Creative Commons
Qu Li, Chi Zhou, Zhen‐Ping Zou

et al.

Synthetic and Systems Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

In situ imaging diagnosis and precise treatment of deep tumor tissues are hotspots in life sciences medical research. recent years, using focused ultrasound to remotely control engineered bacteria for drug release has become one the methods vivo delivery. However, non-visualized pose challenges within body. Therefore, there is an urgent need bacterial vector capable tissue precisely locate vivo. Acoustic reporter genes (ARGs) biological elements used imaging, with gene clusters over 8 kb. ARGs often tested on plasmids, which hinders stable expression limits space inserting components that regulate release. we attenuated Salmonella typhimurium VNP20009, known its tumor-targeting ability, as chassis bacteria. By CRISPR-Cas9 technology, inserted into genome optimized promoter strength copy number ARG expression, constructing ultrasound-visible expressing gas vesicles genome. Additionally, by knocking out stress protein htrA increased maximum injection dose tenfold specificity a hundredfold. The constructed can stably synthesize output signals while directly carrying plasmids therapy. Our research provides effective treatment.

Language: Английский

Programmable Bacteria with Dynamic Virulence Modulation System for Precision Antitumor Immunity DOI Creative Commons
Leyang Wu, Lin Li,

Liyuan Qiao

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 26, 2024

Engineered bacteria-mediated antitumor approaches have been proposed as promising immunotherapies for cancer. However, the off-target bacterial toxicity narrows therapeutic window. Living microbes will benefit from their controllable immunogenicity within tumors safer applications. In this study, a genetically encoded microbial activation strategy is reported that uses tunable and dynamic expression of surface extracellular polysaccharides to improve biocompatibility while retaining efficacy. Based on screening genes associated with Salmonella survival in macrophages, novel attenuated chassis strain AIS (htrA gene-deficient) highly enriched after administration rapidly cleared normal organs are reported. Subsequently, an engineered strain, AISI-H, constructed based optimized quorum-sensing regulatory system. The AISI-H can achieve recovery tumor-specific virulence through HTRA-RCSA axis-based synthetic gene circuit-mediated increase polysaccharide content. These strains act "off" avoid unwanted immune "on" precise tumor suppression mice. shows significant inhibition potent anticancer immunity melanoma mouse model. exhibits excellent biocompatibility. This regulation expands applications microbe-based therapeutics.

Language: Английский

Citations

4
Surface-Functionalized Bacteria: Frontier Explorations in Next-Generation Live Biotherapeutics DOI
Jianqing Jiang, Fanhui Kong, Qi Lei

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 317, P. 123029 - 123029

Published: Dec. 15, 2024

Language: Английский

Citations

4
Leveraging Microorganisms to Combat Skin Cancer DOI Creative Commons

Hayden J. Oyler,

Austen W. Callister,

Makenzi N. Kutch

et al.

Microorganisms, Journal Year: 2025, Volume and Issue: 13(2), P. 462 - 462

Published: Feb. 19, 2025

Skin cancer, including melanoma and non-melanoma types, presents a significant growing global health challenge due to its increasing incidence mortality rates. While conventional treatments such as surgical excision, immunotherapy, targeted therapies are well-established, microorganism-based approaches represent an innovative promising alternative. These employ live, genetically engineered, or commensal bacteria, viral vectors, bacterial components achieve various therapeutic mechanisms, tumor targeting, immune system modulation, vascular disruption, competitive exclusion, drug delivery, direct oncolysis. Despite their potential, these require further investigation address safety concerns, optimize treatment protocols, gain comprehensive understanding of long-term outcomes.

Language: Английский

Citations

0
Development of Ultrasound-Visualized Tumor-Targeting Engineered Bacteria for Precise Tumor Therapy DOI Creative Commons
Qu Li, Chi Zhou, Zhen‐Ping Zou

et al.

Synthetic and Systems Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

In situ imaging diagnosis and precise treatment of deep tumor tissues are hotspots in life sciences medical research. recent years, using focused ultrasound to remotely control engineered bacteria for drug release has become one the methods vivo delivery. However, non-visualized pose challenges within body. Therefore, there is an urgent need bacterial vector capable tissue precisely locate vivo. Acoustic reporter genes (ARGs) biological elements used imaging, with gene clusters over 8 kb. ARGs often tested on plasmids, which hinders stable expression limits space inserting components that regulate release. we attenuated Salmonella typhimurium VNP20009, known its tumor-targeting ability, as chassis bacteria. By CRISPR-Cas9 technology, inserted into genome optimized promoter strength copy number ARG expression, constructing ultrasound-visible expressing gas vesicles genome. Additionally, by knocking out stress protein htrA increased maximum injection dose tenfold specificity a hundredfold. The constructed can stably synthesize output signals while directly carrying plasmids therapy. Our research provides effective treatment.

Language: Английский

Citations

0