• Background

Oligonucleotides, short DNA or RNA sequences, play a pivotal role in modern biotechnology and medicine. Oligonucleotides serve as essential tools in molecular biology, personalized medicine, and therapeutic interventions. Their demand has surged due to advancements in gene therapy, CRISPR-based technologies, and RNA-based therapeutics. Yet, the existing synthesis methods have limitations that hinder scalability, cost-effectiveness, and overall accessibility.

• Challenges in Conventional Oligonucleotide Synthesis

1. Low Yield: Traditional solid-phase synthesis yields can be disappointingly low, especially for longer sequences. Coupling efficiencies, purification steps, and side reactions contribute to reduced overall yield.
2. Time-Consuming: The stepwise nature of solid-phase synthesis prolongs production timelines. Each nucleotide addition requires deprotection, coupling, and purification, leading to days or even weeks for large-scale synthesis.
3. Costly Reagents: Phosphoramidites, protecting groups, and other reagents are expensive. High reagent costs directly impact the final product price.
4. Purification Challenges: Purification methods (HPLC, PAGE) are resource-intensive and may not fully remove impurities, affecting product quality.
5. Environmental Impact: Large-scale oligonucleotide production generates substantial waste, including hazardous chemicals.

• The Game-Changing Technology

Our novel approach addresses these challenges head-on. Here’s how:

1. Enzymatic Synthesis: We employ enzymatic methods, leveraging polymerases and ligases. These enzymes exhibit high specificity, allowing for highly efficient and cost-effective nucleoside production.
2. Parallelization: Our technology enables parallel synthesis of multiple oligonucleotide segments simultaneously. This significantly reduces production time.
3. Liquid-Phase Oligonucleotide Synthesis: By integrating liquid-phase oligonucleotide synthesis, we overcome the scaling limitation of solid-phase chemistry. This dramatically reduces the equipment and material cost associated with SPOS.
4. GalNAc Cluster Compounds: We utilize novel GalNAc cluster design and synthetic strategies to efficiently construct effective delivery system for oligonucleotide therapeutics.
5. AI-Driven Optimization: Machine learning algorithms fine-tune reaction conditions, maximizing yield and minimizing waste.

• Benefits

1. Increased Yield: Our method consistently delivers higher yields, reducing the need for costly re-synthesis.
2. Cost Savings: Reduced reagent usage, shorter production cycles, and streamlined purification translate to significant cost savings.
3. Eco-Friendly: Highly efficient processes minimize chemical waste, aligning with sustainable practices.
4. Scalability: Enzymatic synthesis and liquid-phase oligonucleotide synthesis allows seamless scale-up for large quantities.
5. Clinical Impact: Faster, cost-effective oligonucleotide production accelerates drug development and personalized medicine.