Mir-375- and Mir-1-Regulated Coxsackievirus B3 Has No Pancreas and Heart Toxicity but Strong Antitumor Efficiency in Colorectal Carcinomas

Simple SummaryContent extracted from patent full text and abstract with AI.

This invention describes a genetically engineered version of Coxsackievirus B3 (CVB3), a virus known for its natural cancer-killing properties (oncolytic activity), that has been modified for safer use in cancer therapy, particularly for colorectal cancer. The CVB3 genome is engineered to include target sequences for tissue-specific microRNAs (miR-375 for pancreas and miR-1 for heart), effectively preventing the virus from replicating in the pancreas and heart and thus abolishing its toxicity to these organs, while retaining strong anti-cancer effects within tumors. This construct or resulting virus can be delivered as a pharmaceutical composition for selective cancer treatment without harming vital non-tumor tissues.

Use CasesContent extracted from patent full text and abstract with AI.

• Treatment of colorectal cancer using oncolytic virus therapy.
• Potential use for other solid tumors or tumor types where miR-375 and miR-1 are not abundantly expressed in the cancer cells, but are present in healthy tissues to prevent viral toxicity.
• Development of safer oncolytic virotherapy regimens for cancer patients.
• Combination therapies with conventional treatments (chemotherapy, immunotherapy) to enhance tumor targeting with reduced systemic side effects.
• Creation of more tumor-selective viral vectors for research or therapeutic purposes.

BenefitsContent extracted from patent full text and abstract with AI.

• Greatly improved safety profile by eliminating off-target organ (pancreas and heart) toxicity, a significant issue with previous oncolytic virus therapies.
• Efficient and selective tumor cell killing, preserving healthy tissue.
• Ability to tailor the virus for specific tumor types by choosing appropriate microRNA targets according to tissue expression profiles.
• Potential for repeated dosing, better survival outcomes, and fewer side effects compared to non-targeted oncolytic viruses.
• Production method (using infectious cDNA) improves purity, consistency, and safety of the therapeutic agent, facilitating manufacturing and regulatory compliance.

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Patent Abstract

The present invention related to an infectious complementary DNA (cDNA) construct characterized in that the cDNA comprises: - the cDNA of the CVB3 genomic RNA sequence of a Coxsackievirus B3 (CVB3); - at least one or more microRNA target sequences (miR-TS), which are complementary to one or more microRNAs having tissue-specific expression pattern, wherein the at least one or more miR-TS are integrated immediately adjacent of the 5´UTR and/or the 3´UTR of the CVB3 protein coding sequence.