Recombinant NDV Expressing VEGF-Trap for Oncolytic Cancer Therapy
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Solution Overview
Problem
Current oncolytic viruses, such as Newcastle disease virus (NDV), have limited therapeutic effects and high side effects due to low response rates and tumor inhibition rates, necessitating the development of recombinant NDV expressing exogenous proteins with anti-tumor activity to enhance efficacy and reduce side effects.
Innovation Solution
Integration of VEGF-Trap and Angiostatin encoding genes into the Newcastle disease virus genome to create a recombinant oncolytic virus (rNDV-VEGF-Trap) that replicates effectively in cancer cells while maintaining safety for non-cancer cells, with VEGF-Trap located between the P and M genes of the NDV genome.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If Newcastle disease virus is used as a single drug for cancer treatment, then the treatment can be simple and easy to administer, but the therapeutic effect is limited with low response rates and tumor inhibition rates
Solution Approach 1:
The patent combines NDV with exogenous anti-tumor genes (VEGF-Trap and Angiostatin) to create a recombinant virus that performs multiple functions simultaneously: oncolysis and anti-angiogenesis, thereby improving therapeutic effect while maintaining ease of administration as a single agent
Solution Approach 2:
The recombinant NDV incorporates foreign gene sequences into its genome, creating a composite viral structure that combines the properties of wild-type NDV with anti-angiogenic factors, resulting in enhanced anti-tumor activity
2Reliability
If recombinant NDV expressing exogenous proteins is developed to enhance anti-tumor efficacy, then the therapeutic effect is improved, but the device complexity and manufacturing difficulty increase
Solution Approach 1:
The patent inserts exogenous genes into specific locations within the NDV genome (between P and M genes), segmenting the viral genome into functional regions that can be independently analyzed and manipulated, facilitating the development of recombinant viruses with enhanced efficacy
Solution Approach 2:
The patent modifies the viral genome by incorporating foreign gene sequences, changing the genetic parameters of NDV to express anti-angiogenic proteins, thereby enhancing anti-tumor efficacy without fundamentally altering the viral structure
3Reliability
If anti-angiogenic therapy is used to inhibit tumor growth, then the tumor growth and metastasis are blocked, but significant therapeutic side effects occur
Solution Approach 1:
The patent achieves localized anti-angiogenic activity by expressing VEGF-Trap and Angiostatin specifically within the tumor microenvironment through viral infection, concentrating the therapeutic effect at the tumor site while reducing systemic side effects
Solution Approach 2:
The recombinant NDV acts as a delivery intermediary that transports anti-angiogenic genes directly to tumor cells, enabling localized drug delivery and reducing the need for high systemic doses that cause side effects
Data Source
AI summary
The present application discloses a recombinant Newcastle disease virus genome, a recombinant Newcastle disease virus rNDV-VEGF-Trap containing the genome and a preparation method therefor, a DNA molecule encoding the recombinant Newcastle disease virus genome, and a use of the genome and the recombinant Newcastle disease virus in the preparation of a drug for treating cancer. The recombinant Newcastle disease virus provided by the present application relates to inserting a coding gene of VEGF-Trap into the genome of the recombinant Newcastle disease virus, such that the recombinant Newcastle disease virus obtained therefrom is replicated with a strong replication capability, thereby killing host cancer cells; moreover, the recombinant Newcastle disease virus has reliable safety for non-cancer cells, and shows improved anti-tumor effect and oncolytic efficiency.