Current Projects
Gene Therapy Vector Platforms
M13 iPhAGE Platform Optimization
The iPhAGE system is an advanced, bacteriophage-based gene delivery platform engineered to overcome critical limitations in current gene therapy, including safety, efficiency, and production challenges. iPhAGE ensures the targeted delivery of highly pure, minimized DNA vectors, free from immunogenic bacterial elements. It shows enhanced gene expression and targeted cellular uptake.
We continue to optimize and improve our scalable, cost-effective platform to further enhance its efficiency, efficacy, and broad therapeutic potential across numerous applications.
Novel Anellovirus-Based Vector Biomanufacturing Production Platform
This is a novel, highly efficient, and cost-effective production platform for anellovirus-based gene therapy vectors. Utilizing an E. coli-based production system, this system enables the scalable production of highly pure, circular ssDNA vectors encapsidated within anellovirus capsid proteins, termed “anellomids.” Anellomids provide superior gene expression and potential redosability, and effectively addresses critical gene therapy limitations, including safety concerns, manufacturing complexity, and suboptimal transgene expression, thus positioning them as a promising solution for broad therapeutic applications.
Novel Adeno-Associated Virus Biomanufacturing Production Platform
Adeno-associated virus (AAV) is an unenveloped virus known for its ability to effectively and securely transport genetic material into cells, making it valuable for gene therapy. Although industrial manufacturing methods for AAV vector production have advanced, challenges remain in terms of quality and production costs, hindering wider development.
The limited scalability of current methods has resulted in prohibitively high costs for many patients seeking AAV gene therapy. We seek to develop a novel AAV vector production method to mitigate these issues.
Applications
Targeted Bacteriophage Gene Delivery to Astrocytes
The filamentous bacteriophage M13 is a single-stranded DNA phage that co-exists with its Escherichia coli host after infection. M13 possesses several attractive characteristics for gene delivery and have a well-documented ability to cross the blood-brain barrier which is an exploitable trait that can be applied to targeted phage delivery to the CNS. Astrocytes have been shown to differentiate into functional neurons. This ability makes them an ideal target for gene delivery and cell transformation.
The goal of this project is to show that intravenous administration of M13 miniphagemids, engineered to carry LCC DNA vectors (iPhAGEs) will effectively cross the blood brain barrier and allow for the reprogramming of astrocytes.
Redosable Gene Delivery Platforms for Retinal Applications
Stargardt Disease, an inherited disease characterized by progressive vision loss, is driven by mutations in the large ABCA4 gene, exceeding the capacity of traditional gene therapy vectors. Our research addresses this with "ministring DNA" (msDNA) minivectors that efficiently deliver the therapeutic ABCA4 gene to the retina.
To further enhance delivery and redosability, we are developing an iPhAGE system utilizing engineered M13 miniphagemids. These phage-based vectors are designed for targeted delivery to photoreceptors offering a promising path for effective and personalized treatment of Stargardt Disease and other ocular disorders.
The Effects of Amyloid-Beta on Neuronal Transcription
Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive decline. The goal of this project was to demonstrate that M13-based miniphagemid vectors could be engineered for targeted gene delivery to neurons, laying foundational groundwork for precise therapeutic interventions in Alzheimer's disease.
M13 miniphagemids were engineered to display Angiotensin IV for neuronal targeting, leveraging its receptor's role in brain delivery. Their genome was also engineered to encode a neural specific promoter, Synapsin 1, for targeted expression, as well as carried a therapeutic gene, ZIP3, or reporter gene, eGFP.
Targeted Miniphagemid Mediated Anti-Angiogenic VLPs
Molecular targeted therapy has emerged as a promising strategy to treat cancer over the last several years. Unlike the broad-spectrum cytotoxic drugs prescribed for conventional chemotherapy, targeted therapy is designed to address specific molecular changes which are unique to a specific cancer type. We developed a system for targeted miniphagemid-mediated delivery of DNA encoding VLPs displaying anti-tumour peptides to tumour cells. We hypothesized that this would then induce the tumor cells to produce HPV VLPs displaying VGB4.
Lambda Phage & Vaccines
Identification of E. coli Host Genes Influencing T4rII Exclusion Phenotype
The rex genes (rexA, rexB) of bacteriophage Lambda (λ) are able to prevent mutant bacteriophage T4rII plaque formation of E. coli hosts lysogenized by λ. The expression of these two genes of the Rex system is primarily regulated by the repressor gene cI from the PM promoter.
This project aims to isolate and identify relevant host mutations that could influence the Rex phenotype. Through this work, the manifestation of Rex has been linked to genes underlying key host stress responses.
Universal Virus-Like Particle for Coronavirus
The human immune system, while capable of generating neutralizing antibodies against pathogens, faces a constant challenge from evolving virus populations, like COVID-19, which generate new strains to evade existing immunity. To address this, we are developing a Universal Virus-Like Particle (UVLP), leveraging a "consensus sequence" derived by averaging genes from closely related coronaviruses. The UVLP is designed to induce a broadly neutralizing antibody response in order to offer durable protection against not just current COVID-19 variants, but also future mutations and emerging coronaviruses.
Development of a Lambda Phage-Based Hybrid Vaccine Platform
More information to come.