ministring DNA (msDNAᵀᴹ) Platform

msDNA carries a highly versatile expression cassette that can be tailored to accommodate promoters, genes of interest and regulatory sequences

Plasmids, along with other DNA vectors, such as minicircles and linear derivatives, play a central role as starting materials, intermediates, drug substances, and drug products in the manufacturing of various therapeutics. These applications encompass DNA and mRNA vaccines, gene-editing templates, and gene therapies employing both viral and non-viral vectors.

msDNAᵀᴹ Features

msDNAᵀᴹ is a highly adaptable platform designed to have a high degree of customizability, accommodate large mono- or poly-cistronic genetic payloads, and be effective across a range of applications and tissue targets and with a size up to 20-25 kb.
msDNAᵀᴹ has demonstrated prolonged and durable gene expression even after single systemic injection, when compared to conventional plasmid vectors. msDNA’s proprietary Super Sequences (SSeq) enhance cellular trafficking & nuclear uptake
msDNAᵀᴹ has a strong safety profile, due to the absence of immunogenic pathogenic sequences, linear conformation and proprietary sequence design. msDNAᵀᴹ has demonstrated increased tolerability and redosability; it also features an in-built safety switch that prevents potentially oncogenic chromosomal integration.

Transgene expression from the msDNA^TM vector in vivo can be sustained and/or increased by re-dosable administration.

When redosability & efficacy of msDNA^TM were evaluated in a dose-dependent study for 16 weeks after multiple injections (3x):

msDNA^TM showed higher and more consistent Luciferase expression compared to the plasmid DNA control
msDNA^TM showed smooth and incremental reaction to injections
msDNA^TM might provide control over dose-response

*msDNAᵀᴹ permits systemic redosability and has durable gene expression after multiple dosing*

Sustained transgene expression in vivo of reporter gene test article: Luciferase expression in BalbC mice after intravenous administration of 2.0 mg/kg of a msDNA^TM vector into the tail vein at a first time point (day 0) and re-dosed with administration of a 3.0 mg/kg msDNA^TM vector at a second time point of 7 days and a third dose of 3.0 mg/kg msDNA^TM on 21 days. Six arm study (n=5 per arm): 1. msDNA^TM-LNP, 2. parental plasmid-LNP, 3. naked msDNA^TM, 4. naked Parental plasmid, 5. control #1: empty LNP, 6. control #2: PBS

msDNAᵀᴹ Product Differentiation

Nafissi N, Slavcev R. Construction and characterization of an in-vivo linear covalently closed DNA vector production system. Microb Cell Fact. 2012 Dec 6;11:154. doi: 10.1186/1475-2859-11-154. PMID: 23216697; PMCID: PMC3540006.

msDNA’s unique combination of linear topology and in vivo production positions it as the highest quality plasmid product available.

Versatility of Applications

msDNA^TM can be used in a wide array of applications, serving as a versatile tool in various fields. msDNA^TM serves as a premium starting material for ex vivo cell therapy applications and for the manufacture of mRNA, lentiviral, and rAAV vectors, ensuring high-quality outcomes across diverse biotechnological endeavors. msDNA also functions as a drug substance for gene addition, in vivo gene editing, and DNA vaccines.

DNA Fidelity: The Importance of Quality Starting Materials & Drug Substances

Plasmids, along with other DNA vectors such as minicircles and linear derivatives, play a central role as starting materials, intermediates, drug substances, and drug products in the manufacturing of various therapeutics.

The quality of starting material plays a pivotal role in determining final product quality. The Mediphage team recently published a study examining the fidelity of DNA replication using enzymatic methods ( in vitro ) compared to plasmid DNA produced in vivo in E. coli , using a novel assay with greater sensitivity than next-generation sequencing.

Our findings show that DNA production in E. coli results in significantly fewer loss-of-function (LOF) mutations (80- to 3,000-fold less) compared to enzymatic (in vitro) DNA replication methods, meaning DNA synthesized in vitro has a significantly higher mutation rate than DNA produced traditionally in E. coli. in vitro enzymatically produced DNA in biotechnology and biomanufacturing may introduce a substantial number of mutation impurities, potentially affecting the quality and yield of final pharmaceutical products, while using DNA starting material derived from E. coli substantially mitigates this risk. -->

Using high-quality materials in the manufacture of genetic medicines is critical in reducing patient risks due to mutations, but can further increase potency (lower doses) and improve production yield and efficiency (reduce cost).

msDNA can be used in a wide array of applications, serving as a versatile tool in various fields. msDNA serves as a premium starting material for ex vivo cell therapy applications and for the manufacture of mRNA, lentiviral, and rAAV vectors, ensuring high-quality outcomes across diverse biotechnological endeavors. msDNA also functions as a drug substance for gene addition, in vivo gene editing, and DNA vaccines.

Programs & Partnering Opportunities

Mediphage has an active non-viral gene therapy development pipeline. Click here to learn more about Mediphage’s therapeutic development programs and the advantages of non-viral gene therapy

Additionally, Mediphage is actively engaging partners interested in evaluating ministring DNA through joint feasibility studies which can lead to msDNA as part of a therapeutic solution.

Collaboration opportunities exist in the areas of non-viral gene therapy, ex vivo cell therapy, in vivo gene editing, msDNA as a starting materials for mRNA or viral vector production, and DNA vaccines. If you are interested in working together to bring novel therapeutics to patients in need, we want to hear from you.