How to find the chemical modification of Cemdisiran?

Cemdisiran, a groundbreaking therapeutic agent, is a small interfering RNA (siRNA) developed by Alnylam Pharmaceuticals in collaboration with Sanofi. This innovative medication targets complement component 5 (C5), a key protein in the complement system, and is specifically indicated for the treatment of geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD). GA is a progressive and irreversible condition that leads to the loss of central vision, significantly impacting the quality of life for affected individuals.

Summary of Research Progress of Cemdisiran

The research progress of Cemdisiran has been marked by significant advancements and milestones. Mechanistically, Cemdisiran operates through RNA interference (RNAi), a natural cellular process that can silence specific genes. By targeting the mRNA of C5, Cemdisiran reduces the production of the C5 protein, which plays a critical role in the activation of the complement system. The complement system is part of the immune response and, when overactivated, can lead to inflammation and tissue damage, contributing to the progression of GA. By reducing C5 levels, Cemdisiran aims to inhibit the complement cascade, thereby reducing inflammation and slowing the progression of GA. This targeted approach addresses the underlying pathophysiology of the disease, offering a more comprehensive and sustainable treatment option compared to current therapies.

Cemdisiran has not yet received regulatory approval, but it is currently in advanced stages of clinical development. The drug has shown promising results in early-phase clinical trials, demonstrating significant reductions in the rate of GA progression and favorable safety profiles. Alnylam Pharmaceuticals and Sanofi have initiated Phase III trials to further evaluate the efficacy and safety of Cemdisiran in larger patient populations. These trials are expected to provide robust data to support potential regulatory submissions in the coming years.

Globally, the competition in the GA treatment market is limited, given the complexity and severity of the condition. Current treatments for GA are primarily supportive, focusing on symptom management and lifestyle adjustments. Cemdisiran, with its novel mechanism of action and targeted delivery, offers a unique and potentially superior treatment option. The drug's ability to achieve sustained reductions in C5 levels with a less frequent dosing schedule makes it an attractive alternative for patients and healthcare providers. The success of Cemdisiran could significantly impact the management of GA, providing a much-needed therapeutic option for a condition with few effective treatments.

Sequence Information and Characteristics of Cemdisiran

The sequence information and characteristics of Cemdisiran are essential to understanding its mechanism of action and therapeutic potential. Cemdisiran is a chemically modified siRNA that targets the mRNA of C5. The siRNA is designed to be a double-stranded RNA molecule, each strand 22-25 nucleotides long. The sequence of the siRNA is meticulously engineered to ensure high specificity and affinity for the target mRNA, minimizing off-target effects and maximizing therapeutic efficacy. The antisense strand of the siRNA hybridizes with the C5 mRNA, leading to its degradation and silencing of the C5 gene.

One of the key features of Cemdisiran is its conjugation to a trivalent N-acetylgalactosamine (GalNAc) ligand, which facilitates liver-specific delivery. The GalNAc-siRNA conjugate is recognized by the asialoglycoprotein receptor (ASGPR) on hepatocytes, enabling efficient uptake and intracellular processing. This targeted delivery system ensures that the siRNA reaches its intended site of action, the liver, where C5 is predominantly expressed. The GalNAc conjugation also enhances the stability and bioavailability of the siRNA, allowing for a more potent and durable therapeutic effect.

Chemical Modification and Action of Cemdisiran

The chemical modifications of Cemdisiran further enhance its stability and efficacy. The siRNA component undergoes several modifications, including 2'-O-methoxyethyl (MOE) substitutions on the ribose sugar of certain nucleotides. These modifications increase the resistance of the siRNA to degradation by nucleases in the bloodstream, thereby extending its half-life and improving its stability. Additionally, the GalNAc conjugation improves the solubility and pharmacokinetic properties of the siRNA, allowing for a more stable and effective therapeutic molecule.

The action of Cemdisiran is mediated through the RNA interference (RNAi) pathway. Once inside the hepatocytes, the GalNAc-siRNA conjugate is processed by the RNA-induced silencing complex (RISC). The passenger strand of the siRNA is degraded, while the guide strand remains bound to the RISC. The guide strand then hybridizes with the complementary C5 mRNA, leading to its cleavage and degradation. This process effectively silences the C5 gene, reducing the production of C5 protein and inhibiting the complement cascade. The reduction in C5 levels is sustained over time, providing long-lasting therapeutic benefits and slowing the progression of GA.

Summary and Prospect

In summary, Cemdisiran represents a significant breakthrough in the treatment of geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD). Its targeted mechanism of action, involving the silencing of C5 mRNA, offers a novel and effective approach to managing this condition. The drug's favorable safety profile, combined with its convenient dosing schedule of once-every-six-weeks subcutaneous injections, makes it an attractive option for patients with GA. With ongoing Phase III trials and strong preclinical and early-phase clinical data, Cemdisiran is poised to play a crucial role in the future of GA treatment. Ongoing research and development efforts aim to further optimize the drug's therapeutic potential and explore its use in other related conditions, opening up new possibilities for patients suffering from ocular diseases and inflammatory disorders. The success of Cemdisiran not only highlights the potential of RNAi technology but also paves the way for the development of similar therapies for a wide range of diseases. As the field of RNAi continues to evolve, Cemdisiran stands as a testament to the innovative approaches being developed to address unmet medical needs and improve patient outcomes.

How to find the chemical modification of all siRNAs?

In Patsnap Bio, you can find the sequence and latest research and development advances of all siRNAs.

Taking Cemdisiran as an example, first click on the Drug/Gene Index on the Patsnap Bio homepage. Here you can search for sequence information by drug and gene names. Enter ' Cemdisiran ' in the search box and click to view the details. On the details page, you can find the basic information and research progress of Cemdisiran.

Click "View all related sequences" below the sequence information to search for and retrieve all biological sequences similar to this information. 

Clicking on the sequence name will provide you with all the basic information of that sequence.

Additionally, a visual diagram of the sequence's chemical modifications is available for immediate access.

Patsnap Bio helps you turn weeks into minutes with cutting-edge AI-enabled tools built to master the complexities of sequence retrieval and automate IP analysis with precision and ease.