Phage-Derived Particles for In Situ C. Acnes Gene Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for genetic modification of Cutibacterium acnes strains are inefficient and limited to specific strains due to the lack of robust replicative DNA vectors and the challenge of delivering genetic material in situ, with electroporation being the only described method, which is performed in vitro.
Innovation Solution
Development of Cutibacterium acnes phagemids and phage-derived particles containing recombinant DNA vectors with phage packaging signals, allowing for in situ genetic modification by transduction, including CRISPR-Cas systems for targeted genome editing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If electroporation is used for genetic modification of C. acnes, then genetic material can be delivered into C. acnes cells, but the method is limited to in vitro conditions and has low efficiency
Solution Approach 1:
The patent uses phage-derived particles as an intermediary vehicle to deliver DNA payloads into C. acnes cells. These particles act as mediators that can transport genetic material across the bacterial cell envelope, enabling both in vitro and in situ genetic modification with high efficiency, thus resolving the limitation of electroporation methods
2Adaptability or versatility
If replicative DNA vectors are developed for C. acnes, then broad-range genetic modification becomes possible, but the complexity of vector design and delivery increases
Solution Approach 1:
The patent develops universal phage-derived particle delivery systems that can transduce multiple C. acnes strains and species. The system uses phage packaging signals and capsid proteins that recognize conserved surface structures across different C. acnes variants, enabling broad-range genetic modification without requiring strain-specific optimization, thus achieving versatility without proportional increases in complexity
Solution Approach 2:
The phage-derived particles utilize natural phage infection mechanisms and bacterial cellular machinery for their own delivery function. The particles self-assemble with phage capsid proteins and use natural transduction pathways to deliver DNA payloads, reducing the need for complex external delivery equipment or procedures
Data Source
AI summary
The invention relates to C. acnes carrying DNA vectors with a C. acnes phage packaging signal and a gene of interest. The invention encompasses a C. acnes producer cell carrying DNA vectors, with a C. acnes phage packaging signal and a gene of interest, for the production of phage-derived particles that can robustly transduce C. acnes receiver cell allowing transgene expression. The invention encompasses C. acnes phage-derived particles carrying these vectors, C. acnes containing these vectors or modified by transduction of these phage-derived particles, and methods of using these phage-derived particles.