NucleoDelivery™ Platform

A next-generation, biodegradable polymer platform that redefines nucleic acid delivery with superior efficiency and minimal toxicity.

Platform Overview

NucleoDelivery™ Platform: Next-Generation Polymer-Based Nucleic Acid Delivery System

The clinical translation of gene therapy has long been hindered by a critical dilemma: delivery systems either lack sufficient transfection efficiency or carry unacceptable toxicity. To overcome this bottleneck, Protheragen proudly introduces our NucleoDelivery™ platform. This innovative technology is built upon a novel lactic-co-glycolic acid-modified polyethylenimine (LGA-PEI) polymer that spontaneously assembles into nanoparticles with various nucleic acids. By integrating the high transfection capability of PEI with the biocompatibility and biodegradability of PLGA, NucleoDelivery™ provides a robust and versatile solution for the delivery of DNA, RNA, and oligonucleotides, demonstrating exceptional safety and potency across diverse cell types and validated in multiple in vivo models.

Disruptive Technology
Excellent Team
Diversified Pipeline
Customized Solutions

Platform Core

LGA-PEI Polymer for High-Efficiency Nucleic Acid Delivery

The NucleoDelivery™ platform is based on a novel polymer (LGA-PEI, ~42.6 kDa) created by covalently linking single lactic-co-glycolic acid (LGA) units to branched polyethylenimine (PEI, 25 kDa) via an amide bond. This unique design preserves the high cationic charge density of PEI, which is essential for efficient nucleic acid condensation and endosomal escape via the “proton sponge” effect. Concurrently, the grafted LGA units shield the positive charge of PEI, significantly reducing nonspecific interactions with cell membranes and serum proteins. This dual-action mechanism results in nanoparticles that are stable, less cytotoxic, and highly effective at delivering genetic material.

Workflow of NucleoDelivery™ Platform

Polymer-Nucleic Acid Complexation

The NucleoDelivery™ polymer is mixed with nucleic acids (plasmid DNA, mRNA, miRNA, or oligonucleotides) in an aqueous solution. Through electrostatic interactions, the polymer condenses the nucleic acids, spontaneously forming uniform nanoparticles (typically 50–150 nm in size).

Cellular Uptake & Endosomal Escape

The positively charged nanoparticles are efficiently internalized by target cells via endocytosis. The polymer’s buffering capacity promotes rapid endosomal escape, releasing the intact nucleic acid cargo into the cytoplasm before lysosomal degradation.

Cargo Release & Expression

Once in the cytoplasm, the nucleic acid is released from the polymer complex. DNA is transported to the nucleus for transcription, while RNA is immediately available for translation or functional activity.

Biodegradation & Clearance

The polymer backbone incorporates biodegradable LGA units, facilitating breakdown and safe clearance from the body, thereby minimizing long-term toxicity.

Platform Advantages

Unique Advantages of the NucleoDelivery™ Platform

Superior Transfection Efficiency

The NucleoDelivery™ platform demonstrates high transfection efficiency in a wide range of cells, including hard-to-transfect lines such as Jurkat (T-cell leukemia) and THP-1 (monocytic) cells, as well as primary cells like fibroblasts and stem cells. In comparative studies, its performance is superior or comparable to leading commercial reagents like Lipofectamine 2000, but with significantly lower cytotoxicity.

Drastically Reduced Cytotoxicity

By shielding the PEI core with LGA units, the platform minimizes the membrane disruption and mitochondrial damage typically associated with unmodified PEI. In vitro assays show that NucleoDelivery™ nanoparticles maintain high cell viability at doses where PEI alone causes significant cell death. In vivo, the maximum tolerated dose is over four times higher than that of unmodified PEI, enabling safer systemic administration.

Versatile Nucleic Acid Cargo Compatibility

The NucleoDelivery™ platform is highly versatile, capable of delivering a broad spectrum of genetic materials. It efficiently packages and delivers plasmid DNA (including large constructs up to ~200 kb), modified mRNA (mmRNA), double-stranded miRNA mimics, and DNA oligonucleotides, making it a single, unified solution for diverse gene therapy and cell engineering applications.

Proven In Vivo Efficacy

In xenograft mouse models, NucleoDelivery™ nanoparticles demonstrated efficient delivery of plasmid DNA and miRNA mimics to targeted tumors (pancreatic and ovarian) and major organs (liver, spleen, pancreas) after systemic or intratumoral administration. Crucially, these high delivery efficiencies were achieved with a safety margin that far exceeds that of traditional PEI-based systems, marking a significant step toward clinical translation.

Platform Application

Accelerating Advanced Nucleic Acid Therapeutic Development

In Vitro Cell Engineering & Transfection

The NucleoDelivery™ platform serves as a superior tool for research and process development, enabling highly efficient and low-toxicity transfection of challenging cell lines ( e.g., Jurkat, THP-1, HUVECs) and primary cells for gene function studies, CAR-T cell engineering, and stable cell line generation.

In Vivo Gene Therapy

With its significantly improved safety profile and proven systemic delivery capability, the platform is ideally suited for in vivo gene therapy applications. It can effectively deliver therapeutic plasmid DNA or mRNA to target organs such as the liver, spleen, and pancreas via intravenous administration.

Functional Biomaterials & Cosmeceuticals

RNA-Based Therapeutics

The platform’s ability to efficiently deliver double-stranded RNA ( e.g., miRNA mimics) and modified mRNA positions it as a powerful delivery vehicle for next-generation RNA therapeutics, including mRNA vaccines and miRNA-based cancer treatments.

Tumor-Targeted Nucleic Acid Delivery

NucleoDelivery™ nanoparticles effectively deliver therapeutic genes and RNAi agents to solid tumors, as demonstrated in pancreatic and ovarian cancer xenograft models. This capability supports the development of targeted cancer therapies, including tumor suppressor gene replacement and oncolytic nucleic acid strategies.

Pipeline

Research & Development Pipeline

Projects	Therapy Type	Target	Indication
EPX008	mRNA Vaccine	SARS-CoV-2 Spike Protein	COVID-19
EPX011	DNA Therapy	p53 Tumor Suppressor	Pancreatic Cancer
EPX014	miRNA Therapy	miR-520h	Ovarian Cancer
EPX017	Oligonucleotide	STAT3 Antisense	Solid Tumors

Get in Touch with Us

FAQs

Frequently Asked Questions

Q1: What types of nucleic acids can the NucleoDelivery™ platform deliver? A: The platform is highly versatile and can deliver a wide range of nucleic acids, including plasmid DNA (pDNA, up to ~200 kb), modified mRNA (mmRNA), double-stranded miRNA mimics, and DNA oligonucleotides.
Q2: How does the transfection efficiency compare to Lipofectamine 2000? A: In many cell types, including hard-to-transfect suspension cells like Jurkat and THP-1, NucleoDelivery™ demonstrates superior or comparable transfection efficiency. A key advantage is that it achieves this with significantly lower cytotoxicity, resulting in higher overall cell viability and cell density post-transfection.
Q3: What is the size of the nanoparticles formed? A: The NucleoDelivery™ polymer spontaneously self-assembles with nucleic acids to form uniform nanoparticles. The size can be controlled by adjusting the polymer-to-nucleic acid ratio, typically ranging from 50 to 150 nm, which is ideal for cellular uptake and systemic delivery.
Q4: Is the NucleoDelivery™ platform suitable for in vivo applications? A: Yes. It has been successfully used in mouse models for systemic delivery of plasmid DNA and miRNA mimics to tumors and major organs. The platform’s maximum tolerated dose is significantly higher than that of unmodified PEI, making it a safer candidate for in vivo gene therapy.
Q5: Can the NucleoDelivery™ platform be used for large DNA constructs? A: Yes. The platform has demonstrated the ability to successfully deliver a large artificial chromosome DNA of approximately 200 kb into cells, highlighting its capacity for complex gene delivery applications.
Q6: What is the stability of the NucleoDelivery™ polymer? A: The polymer itself is stable. Studies have shown that the polymer stored at room temperature for up to 3 months retains its full nucleic acid delivery capability.