Chimera Polypeptide DNase I Cdt Targeting Neoplastic Cells

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current cancer treatments lack effective methods to inhibit cell proliferation specifically in neoplastic cells, and existing therapies may have limitations in targeting cancerous epithelial cells effectively.

Innovation Solution

Development of recombinant polypeptides comprising a chimera of DNase I and Cdt fragments or their homologues, which can be used to inhibit cell proliferation by contacting neoplastic cells, thereby treating or suppressing neoplastic diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional cancer treatments are used, then general cell targeting is achieved, but specific inhibition of neoplastic cell proliferation is insufficient

Engineering Contradiction:

Improvespecificity of neoplastic cell targetingVSAvoidbroad applicability to different cancer types

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines two distinct functional domains into a single chimera polypeptide: the cell-binding domain from Cdt toxin (providing specificity for neoplastic cells) and the cytotoxic domain from DNase I (providing proliferation inhibition). This merging allows the single molecule to simultaneously achieve specific targeting and effective inhibition, resolving the contradiction between reliability and versatility.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The chimera polypeptide represents a composite protein structure where the N-terminal portion derives from Cdt and the C-terminal portion derives from DNase I. This composite design integrates the cell-binding properties of Cdt with the enzymatic cytotoxic activity of DNase I, creating a molecule that兼具 specificity and potency against diverse neoplastic cells.

Inventive Principle:

Principle #40Composite materials

2Reliability

If recombinant toxins are developed to target specific cells, then cell proliferation inhibition is improved, but treatment complexity increases

Engineering Contradiction:

Improvecell proliferation inhibition efficacyVSAvoidcomplexity of recombinant polypeptide construction

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The chimera polypeptide is constructed by segmenting two parent proteins and joining their functional domains. The Cdt portion provides the binding function while the DNase I portion provides the cytotoxic function. This segmentation allows each domain to maintain its independent function while contributing to the overall efficacy of the recombinant toxin, achieving high proliferation inhibition with manageable complexity.

Inventive Principle:

Principle #1Segmentation

3Reliability

If chimeric proteins are constructed to enhance therapeutic effect, then cancer treatment efficacy is improved, but manufacturing difficulty increases

Engineering Contradiction:

Improvetherapeutic effect against neoplastic diseaseVSAvoidease of recombinant polypeptide production

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The chimera polypeptide design uses universally applicable modular domains that can be produced using standard recombinant protein expression systems. The Cdt binding domain and DNase I cytotoxic domain are both amenable to conventional manufacturing techniques, allowing the chimeric protein to be produced efficiently while maintaining enhanced therapeutic efficacy against neoplastic diseases.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The recombinant polypeptides effectively inhibit cell proliferation and treat neoplastic diseases by targeting cancerous epithelial cells, offering a novel approach to cancer therapy.

Implementation Method 1

Human DNase I has been used as a therapeutic agent... the present invention provides a recombinant polypeptide comprising a chimera, wherein said chimera comprises a DNase I fragment

Methodology Applied

Scientific EffectDNA degradation by DNase I: Enzyme

Implementation Method 2

Cytolethal distending toxin (Cdt) is a genotoxin... that classically arrest the growth of specific types of eukaryotic cells or cell lines at either the G0/G1 or G2/M phase of the cell cycle

Methodology Applied

Scientific EffectCell cycle arrest by Cdt toxin:

Implementation Method 3

Recombinant toxins, hybrid proteins composed of a bacterial toxin and either a growth factor or a portion of a recombinant monoclonal antibody, have received significant attention in cancer therapeutics

Methodology Applied

Scientific EffectCell entry mechanism:

Data Source

PatentUS8920809B2Chimera comprising bacterial cytotoxin and methods of using the same

Publication Date: 2014.12.30 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA

AI summary

This invention provides, a recombinant polypeptide encoding a chimera. The chimera includes a DNase I fragment or a homologue thereof and a Cdt fragment or a homologue thereof. Further, the invention provides methods, utilizing the recombinant polypeptide encoding the chimera, such as a method for inhibiting the proliferation of a neoplastic cell, a method for treating a neoplastic disease in a human subject, a method for inhibiting or suppressing a neoplastic disease in a human subject, and a method for reducing the symptoms associated with a neoplastic disease in a human subject.