Sequence Design

Sequence Design

Over the last three decades, small interfering ribonucleic acids (siRNAs) and antisense oligonucleotides (ASOs) have become powerful tools for modulating the expression of genes in vivo and in vitro. Potential oligonucleotide therapeutics have been discovered and developed with varying degrees of success. However, the development of oligonucleotide therapeutics remains challenging because they often have unexpected off-target effects and low specific binding capacity. These shortcomings may lead to the failure of oligonucleotide therapeutics. Therefore, it is essential to improve the stability of oligonucleotides and the specific binding ability between oligonucleotides and targets during designing oligonucleotides. Alfa Chemistry has a professional oligonucleotide design technology platform, and our approaches enable us to design and identify the sequence of oligonucleotides with high efficacy and specificity in gene silencing, leading to the development of more effective therapeutic candidates.

Considerations in Sequence Design

Many factors need to be considered when designing oligonucleotides, including, but not limited to, the following. These factors need to be weighed according to the intended use of oligonucleotides. For example, compounds designed as in vitro tools only need to be active in a single species, whereas it is important for oligonucleotides to be active in model organisms as well as patients[1].

a. Splice variants.
b. Predicted activity.
c. Secondary structure.
d. Intron/exon boundaries.
e. Undesirable motifs (e.g. Toxic, poly-a).

f. Length of oligonucleotide chain.
g. Cross-species targeting for validation.
h. Single nucleotide polymorphisms (SNPs).
i. Complementarity with off-target sequences.
j. Chemical modification pattern of nucleotides.

Our Advantages

With many years of experience in sequence design of oligonucleotides, Alfa Chemistry is confident to support and promote your oligonucleotide therapeutic projects. Compared with other companies, our sequence design technology platform has many outstanding advantages, including but not limited to the following.

We have a lot of software for oligonucleotide design. For example, siDirect 2.0 for siRNA design; and PFRED for siRNA and ASO design.

Our information technology department has the ability to modify algorithms to optimize design tools for oligonucleotides.

We have a strict set of design principles for each class of oligonucleotide.

We can meet the sequence design requirements of preclinical animals and clinical trials.

We have the ability to design optimal oligonucleotide sequences to improve gene silencing efficiency.

If you have questions about our oligonucleotide sequence design service, please contact us. We are happy to provide you with technical support.

Reference

  1. Sciabola, S.; et al. PFRED: A computational platform for siRNA and antisense oligonucleotides design. PLOS ONE. 2021, 16(1): 238753.

Our products and services are for research use only and cannot be used for any clinical purposes.

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