Introduction of siRNA Off-Target Effects

siRNA off-target effects refer to the unintended and nonspecific silencing of genes other than the intended target due to the sequence similarity between the siRNA and unintended mRNA transcripts. This phenomenon can result in unintended consequences, leading to altered cellular functions and potentially adverse effects. Given the complexity of biological systems and the intricate network of gene interactions, it is imperative to thoroughly assess and minimize off-target effects before proceeding with siRNA-based therapies.

Fig. 1. Types of off-target effects observed with small interfering RNAs. (Jackson, A. L., & Linsley, P. S., 2010)

Reasons for siRNA off-targeting

The causes of siRNA off-targeting are multifaceted. One key factor is the inherent sequence similarity between genes, where a siRNA sequence designed to target a specific gene may also possess partial complementarity to other genes. Additionally, the thermodynamic stability of the siRNA-mRNA duplex and the potential for seed region-mediated interactions contribute to off-target effects. These factors, combined with cellular context and the presence of single nucleotide polymorphisms (SNPs), can lead to unintended gene silencing.

Applications of siRNA Off-Target Effect Assessment

The applications of siRNA off-target effect assessment are diverse and impactful.

• unraveling complex gene regulatory networks.
• validating target gene functions.
• selection of siRNA candidates with minimal off-target effects.
• expediting the development of safe and effective therapies.
• optimization of siRNA delivery methods.

What We Provide?

Creative Proteomics is recognize the significance of siRNA off-target effect assessment in the development of cutting-edge therapeutics. Our state-of-the-art facilities and expert team offer comprehensive services tailored to meet your needs.

Quantitative Analysis

We provide accurate quantitative analysis services, where we are able to determine the concentration of siRNA in a sample to ensure that the appropriate concentration is used for the assessment.

Potency Assessment

We provide comprehensive potency assessment services, we are able to assess the efficacy of siRNAs, test the inhibitory effect of siRNAs on targeted genes, and confirm whether they are effective in reducing gene expression.

Sequence Confirmation of DNA & RNA

We offer comprehensive services for confirming the integrity of sequences, specifically focusing on siRNA. Our aim is to ensure a precise match between the sequence and its designed counterpart. This approach is crucial in order to prevent any misleading outcomes that could arise due to inaccuracies in the siRNA sequence.

Forced Degradation Studies

We conduct thorough stability investigations that replicate the degradation of siRNA molecules under conditions of stress, including scenarios involving elevated temperatures and oxidative environments. The primary objective is to evaluate the resilience of siRNAs and the potential formation of degradation byproducts.

Conclusions

As the utilization of siRNA-based treatments progresses toward potential clinical applications, dealing with the issue of unintended impacts is of utmost importance. By conducting meticulous evaluations and refining the process, we can tap into the complete capabilities of siRNA while minimizing any inadvertent repercussions.

At Creative Proteomics, our array of services is meticulously developed to empower researchers and innovators in their pursuit of gene-silencing approaches that are both safe and efficacious. Should you have any questions or wish to explore opportunities for collaboration, please feel free to contact us.

Our Advantages

• Our team consists of proficient researchers and bioinformatics specialists who possess an in-depth grasp of siRNA biology and the associated off-target effects.
• We employ cutting-edge bioinformatics resources, high-capacity assays, and state-of-the-art apparatus to ensure outcomes that are accurate and dependable.
• Our services are customized to align with your distinct siRNA sequences and research objectives, offering tailored solutions to the unique challenges you face.
• Detailed reports will be furnished, outlining predictions concerning off-target effects, analysis findings, and actionable suggestions for enhancement.
• Safeguarding the confidentiality and security of your data is a top priority for us, guaranteeing that your research data remains shielded throughout the assessment journey.