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Please note that we are not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

miRNA Nucleotide Base Modification

At Protheragen BioNucleics, we specialize in advancing oligonucleotide therapeutics through precision-driven solutions. Our expertise spans Oligonucleotide Drugs CRO, Oligonucleotide Modification Services, and miRNA Modification Services, with a focus on enhancing the stability, specificity, and efficacy of miRNA-based therapies. By integrating cutting-edge technologies, we empower researchers and developers to overcome challenges in RNA therapeutics.

Overview of miRNA Nucleotide Base Modification

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression, making them promising candidates for therapeutic intervention. However, their inherent instability, off-target effects, and inefficient cellular uptake limit clinical utility. Nucleotide base modification addresses these challenges by chemically altering miRNA structures to improve:

Nuclease resistance for prolonged half-life.
Binding affinity for enhanced target specificity.
Cellular delivery efficiency through optimized physicochemical properties.
Modifications such as 2'-O-methyl, locked nucleic acids (LNAs), and phosphorothioate linkages are strategically employed to tailor miRNA functionality.

Our Services: Precision in miRNA Engineering

We deliver comprehensive, innovation-driven services tailored to optimize miRNA functionality for therapeutic and diagnostic applications. Our multidisciplinary approach integrates advanced chemical synthesis, bioinformatics, and formulation science to address the unique challenges of miRNA-based therapies.

Customized Chemical Modifications

We deploy a versatile array of chemical modifications to enhance miRNA stability, specificity, and bioavailability. Our team strategically selects modification patterns based on miRNA sequence, target tissue, and intended therapeutic mechanism, ensuring optimal performance without compromising biological activity.

Functional Group Additions: Site-specific conjugation of biotin, fluorophores, or cholesterol for tracking, imaging, or enhanced cellular uptake.
Bicyclic and Tricyclic Modifications: Novel bridged nucleic acids (BNAs) to achieve ultra-high target affinity while minimizing off-target interactions.

Proprietary Design Algorithms

Leveraging AI and machine learning, our platform accelerates the rational design of modified miRNAs by:

Seed Region Preservation: Identifying critical nucleotides in the miRNA "seed sequence" (positions 2–8) to avoid disruptive modifications.
Off-Target Prediction: Analyzing potential cross-reactivity with non-target mRNAs using multi-omics databases.
Stability Profiling: Simulating thermodynamic and structural impacts of modifications to prioritize configurations with maximal nuclease resistance.
Species-Specific Optimization: Tailoring designs for human, primate, or rodent models to streamline preclinical validation.

Delivery System Optimization

We engineer advanced delivery vehicles to maximize the bioavailability of modified miRNAs. Each system is rigorously tested for payload protection, cellular internalization efficiency, and endosomal escape capabilities.

Lipid Nanoparticles (LNPs): Customized formulations with ionizable lipids, PEGylated components, and pH-sensitive coatings for tissue-specific targeting (e.g., hepatic or neuronal delivery).
GalNAc Conjugates: Triantennary N-acetylgalactosamine (GalNAc) ligands for hepatocyte-selective uptake via asialoglycoprotein receptor (ASGPR) mediation.
Exosome Mimetics: Hybrid vesicles combining synthetic and natural exosome components for low-immunogenicity, and systemic delivery.
Polymer-Based Carriers: Biodegradable poly(lactic-co-glycolic acid) (PLGA) or dendrimer nanoparticles for sustained release.

Analytical and Validation Services

We ensure the integrity and efficacy of modified miRNAs through state-of-the-art characterization:

Structural Confirmation: High-resolution mass spectrometry (HRMS) and NMR to verify modification sites and purity (>95% by HPLC).
In Vitro: Luciferase reporter systems and qRT-PCR to quantify target mRNA repression.
In Vivo: Efficacy studies in disease-relevant animal models, including biodistribution analysis via IVIS imaging.
Safety Profiling: Cytokine release assays (CRAs) and complement activation tests to assess immunogenicity.
Stability Testing: Serum and nuclease resistance assays under physiological conditions.

Frequently Asked Questions

Q1: How do you ensure modified miRNAs retain biological activity?

We employ a dual-strategy approach combining computational precision and empirical validation. Our AI platform identifies modification sites that avoid critical regions essential for target mRNA binding, preserving functional integrity. Modifications are then rigorously tested using in vitro luciferase reporter assays, qRT-PCR for target repression, and in vivo efficacy studies in disease models. Additionally, structural analyses confirm that modifications do not disrupt miRNA secondary structure required for RISC complex incorporation.

Q2: Can you modify miRNAs for specific delivery systems?

Absolutely. We tailor nucleotide modifications to synergize with your chosen delivery platform. Each design is validated through delivery-specific assays, including serum stability testing, cellular uptake imaging, and in vivo biodistribution studies.

Lipid Nanoparticles (LNPs): Incorporate hydrophobic modifications (e.g., cholesterol tagging) to enhance encapsulation efficiency and endosomal escape.
GalNAc Conjugates: Introduce spacer sequences and nuclease-resistant backbones (e.g., PS linkages) to stabilize miRNA-GalNAc complexes during hepatic targeting.
Viral Vectors: Optimize miRNA size and charge via 2'-F/2'-OMe modifications to ensure compatibility with AAV or lentiviral packaging limits.
Polymer-Based Systems: Adjust miRNA hydrophilicity using PEGylated modifications for sustained release from PLGA carriers.

Our services and products are exclusively for authorized organizations in research, development, or manufacturing and are not intended for direct use by individuals or patients or as medical advice, diagnosis, or treatment.