IL-12 Genetic Constructs for DNA Vaccine Immune Potency

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current DNA vaccine technologies face challenges in inducing strong T cell and B cell immunity, with limitations in manufacturing complexity, serological interference, and inadequate immune potency, particularly in human clinical trials, necessitating improved strategies for enhancing immune responses and expression of IL-12 as a potent adjuvant.

Innovation Solution

Development of improved IL-12 gene adjuvants with optimized leader sequences, mRNA stability, and codon optimization to enhance transcription and translation, along with electroporation for improved delivery, facilitating higher potency and bioactivity, thereby increasing the immune response efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If simple plasmid DNA is used as a vaccine platform, then manufacturing complexity is reduced, but immune potency is insufficient to induce satisfactory T cell and B cell immunity

Engineering Contradiction:

Improvemanufacturing complexityVSAvoidimmune potency

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent applies parameter changes by optimizing codon usage, enhancing leader sequences, and modifying mRNA stability elements in the IL-12 gene construct to significantly improve transcription and translation efficiency, thereby achieving high immune potency while maintaining plasmid DNA platform simplicity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite gene construct combining IL-12 p35 and p40 subunits with optimized regulatory elements and codon sequences, forming a enhanced adjuvant composition that delivers both Th1 and Th2 immune responses simultaneously

Inventive Principle:

Principle #40Composite materials

2Reliability

If IL-12 expression is increased to enhance immune response, then immune potency is improved, but dose requirement and manufacturing complexity increase

Engineering Contradiction:

Improveimmune potencyVSAvoidmanufacturing complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

Through systematic optimization of codon usage, leader sequences, and mRNA stability elements, the patent achieves high-level IL-12 expression from minimal plasmid doses, reducing the actual amount of DNA needed while maintaining manufacturing simplicity

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20220193230A1Compositions, comprising improved il-12 genetic constructs and vaccines, immunotherapeutics and methods of using the same

Publication Date: 2022.06.23 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA

AI summary

Nucleic acid molecules and compositions comprising: a nucleic acid sequence that encodes IL-12 p35 subunit or a functional fragment thereof and/or a nucleic acid sequence that encodes IL12 p40 subunit or a functional fragment thereof, are disclosed. The nucleic acid molecules and compositions further comprising a nucleic acid sequence that encodes an immunogen are also disclosed. Method of modulating immune response and methods of inducing an immune response against an immunogen are disclosed. Therapeutic and prophylactic vaccination methods are also disclosed.