التفاصيل البيبلوغرافية
العنوان: |
An intravenous pancreatic cancer therapeutic: Characterization of CRISPR/Cas9n-modified Clostridium novyi-Non Toxic |
المؤلفون: |
Dailey, Kaitlin M., Small, James M., Pullan, Jessica E., Winfree, Seth, Vance, Krysten E., Orr, Megan, Mallik, Sanku, Bayles, Kenneth W., Hollingsworth, Michael A., Brooks, Amanda E. |
المساهمون: |
Venkata Subbaiah, Kadiam C., NIH COBRE, North Dakota State University, University of Nebraska Medical Center, Nebraska Department of Health and Human Services |
المصدر: |
PLOS ONE ; volume 18, issue 11, page e0289183 ; ISSN 1932-6203 |
بيانات النشر: |
Public Library of Science (PLoS) |
سنة النشر: |
2023 |
المجموعة: |
PLOS Publications (via CrossRef) |
الوصف: |
Clostridium novyi has demonstrated selective efficacy against solid tumors largely due to the microenvironment contained within dense tumor cores. The core of a solid tumor is typically hypoxic, acidic, and necrotic—impeding the penetration of current therapeutics. C . novyi is attracted to the tumor microenvironment and once there, can both lyse and proliferate while simultaneously re-activating the suppressed immune system. C . novyi systemic toxicity is easily mitigated by knocking out the phage DNA plasmid encoded alpha toxin resulting in C . novyi -NT; but, after intravenous injection spores are quickly cleared by phagocytosis before accomplishing significant tumor localization. C . novyi -NT could be designed to accomplish intravenous delivery with the potential to target all solid tumors and their metastases in a single dose. This study characterizes CRISPR/Cas9 modified C . novyi- NT to insert the gene for RGD, a tumor targeting peptide, expressed within the promoter region of a spore coat protein. Expression of the RGD peptide on the outer spore coat of C . novyi- NT indicates an increased capacity for tumor localization of C . novyi upon intravenous introduction based on the natural binding of RGD with the α v β 3 integrin commonly overexpressed on the epithelial tissue surrounding a tumor, and lead to immune stimulation. |
نوع الوثيقة: |
article in journal/newspaper |
اللغة: |
English |
DOI: |
10.1371/journal.pone.0289183 |
الإتاحة: |
https://doi.org/10.1371/journal.pone.0289183Test |
حقوق: |
http://creativecommons.org/licenses/by/4.0Test/ |
رقم الانضمام: |
edsbas.12BA03E1 |
قاعدة البيانات: |
BASE |