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Creative Biolabs provides comprehensive nucleic acid-based anti-monkeypox drug discovery solutions. Our strength lies in offering end-to-end services, from target identification to preclinical evaluation, helping customers accelerate the development of innovative and effective antiviral therapeutics.
Monkeypox (Mpox), caused by the Orthopoxvirus MPXV, represents a significant global health challenge. Its complex replication cycle within host cells offers numerous targets for intervention. Traditional antiviral approaches often face limitations such as specificity and resistance. Nucleic acid-based therapies, however, offer a revolutionary alternative. These precision tools directly interact with viral genetic material or essential viral proteins, providing highly targeted mechanisms of action to combat the virus effectively while minimizing off-target effects.
Figure.1 Virus life cycle and possible antiviral mechanism.1
Creative Biolabs leverages its extensive expertise to offer a diverse portfolio of nucleic acid-based solutions for anti-Mpox drug discovery:
Antisense oligonucleotides (ASOs) are designed to precisely bind to critical viral mRNA sequences. This binding mechanism effectively inhibits the translation of essential viral proteins or triggers the degradation of viral mRNA, thereby disrupting the Mpox replication cycle. ASOs are optimized for high specificity and stability.
Catalytic RNA molecules, known as ribozymes, are utilized and engineered for sequence-specific cleavage of target viral RNA. These molecular scissors directly inactivate Mpox viral transcripts, preventing the synthesis of vital viral components and halting the progression of infection with high precision.
Similar to ribozymes, deoxyribozymes (DNAzymes) are synthetic DNA molecules possessing catalytic RNA-cleaving activity. Highly specific DNAzymes are developed to target and hydrolyze Mpox viral mRNA, offering a potent and direct method to disrupt viral gene expression and replication.
Innovative chimeric RNA-DNA molecules, often with modified nucleotides, are explored for their unique ability to interact with specific viral genetic material. These constructs offer enhanced stability and binding affinity, providing a novel and precise avenue for modulating viral gene function and inhibiting Mpox.
RNA interference (RNAi) solutions involve designing small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) to harness the cell's natural gene silencing machinery. These molecules guide the degradation of essential viral mRNAs or host factors hijacked by Mpox, effectively knocking down gene expression vital for viral propagation.
Single-stranded DNA or RNA aptamers are developed that fold into specific three-dimensional structures, allowing them to bind with high affinity to Mpox viral proteins or other critical targets. These "chemical antibodies" can block viral entry, inhibit viral enzymes, or disrupt viral assembly, providing versatile therapeutic candidates.
a. The customer provides preliminary ideas or specific requirements for targets, nucleic acid types (siRNA/ASO/mRNA), application scenarios (treatment/prevention), etc.
b. The expert team communicates in depth with the customer to jointly analyze and confirm the best viral targets (such as key regions on the MPXV genome) or host factor targets.
a. Based on the determined targets, computational biology design is performed to synthesize efficient and specific siRNA and ASO sequences, or to design mRNA sequences and modification schemes.
b. Key technologies such as sequence optimization and chemical modification (to improve stability, delivery efficiency and reduce off-target effects) are emphasized.
a. Required nucleic acid molecules (such as oligonucleotides, mRNA) are efficiently synthesized.
b. Strict quality control measures are performed, including assessments of purity, concentration, sequence verification, and endotoxin detection.
a. Comprehensive evaluations are conducted in a BSL-3 biosafety laboratory using an MPXV-infected cell model. These assays assess the antiviral activity of nucleic acid molecules (e.g., inhibition of viral replication, gene expression, and viral load).
b. The knockdown/knockout efficiency of nucleic acid molecules on target genes (siRNA/ASO) or protein expression levels (mRNA) is detected.
c. Cytotoxicity and off-target effects are evaluated.
a. In vivo delivery and pharmacodynamics validation of nucleic acid molecules are performed in appropriate animal models (such as mice, non-human primates).
b. The stability, distribution, and effects of nucleic acid molecules on the immune system in vivo are monitored.
Comprehensive experimental data, detailed analysis reports, and professional data interpretation and suggestions are provided upon completion of studies.
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Targeted Precision
Our solutions leverage nucleic acids for highly specific targeting of viral mechanisms, minimizing off-target effects.
Comprehensive Modalities
We offer a broad spectrum of nucleic acid types, including ASOs, RNAi, aptamers, ribozymes, deoxyribozymes, and chimeric RNA-DNA molecules.
Integrated Workflow
From design to in vivo validation, our streamlined process accelerates drug discovery timelines.
Biosafety Expertise
All in vitro viral work is conducted in certified BSL-3 facilities, ensuring safety and compliance.
Customized Approach
We tailor every project to client-specific needs, ensuring optimal design and experimental strategies.
Our expert team will guide you through this crucial decision. We consider factors like target accessibility, desired mechanism of action (e.g., gene silencing, protein inhibition), delivery considerations, and existing data to recommend whether siRNA, ASO, mRNA, or another modality is best suited for your specific Mpox therapeutic goal.
Minimizing off-target effects and ensuring safety are paramount. We employ advanced bioinformatics for sequence specificity, incorporate chemical modifications to enhance selectivity, and conduct rigorous in vitro cytotoxicity assays and comprehensive in vivo toxicology studies to thoroughly evaluate and mitigate potential risks.
Yes, our comprehensive services include advanced target identification and validation. Our team can leverage cutting-edge genomics and bioinformatics to pinpoint novel viral or host-factor targets critical for Mpox replication, helping you establish a strong foundation for your drug discovery efforts.
For in vivo pharmacodynamics evaluation, we commonly utilize established animal models such as mice, which can be engineered to be susceptible to Mpox. Additionally, non-human primates may be employed for more advanced studies, providing highly relevant data on efficacy and safety.
While we do not act as a regulatory agency, our team possesses extensive experience in preclinical development and can offer strategic guidance. We assist clients in preparing comprehensive data packages and understanding the requirements for regulatory submissions, facilitating a smoother transition to clinical trials.
Creative Biolabs has deep expertise in nucleic acid chemical modifications. We utilize a wide range of proprietary and established modifications to enhance stability, improve cellular uptake, reduce immunogenicity, and fine-tune pharmacokinetic profiles, optimizing your therapeutic candidates for maximum efficacy.
We implement a stringent multi-stage quality control process for all synthesized nucleic acid molecules. This includes high-resolution analytical techniques to verify purity, precise concentration measurements, comprehensive sequence verification, and rigorous endotoxin detection to ensure the highest quality for your research.
Creative Biolabs is a leading service provider that focuses on drug discovery. We can assist you in designing the best research outline customized to meet the requirements of clients' programs. If you are interested in our services and products, please do not hesitate to contact us for more details.
Reference
We DO NOT PROVIDE ANY PRODUCTS OR SERVICES DIRECTLY TO PATIENTS. All of our products are for Research Use Only (RUO), NOT intended for diagnostic, therapeutic, or clinical use.