Oligonucleotide Drug Toxicity Assessment Service

Most oligonucleotide therapies act through antisense mechanisms and are directed against various RNA species. Lots of antisense oligonucleotides (ASOs) from several classes of molecules are currently in drug development. There are 2 broad categories of potential toxicities for ASOs: hybridization dependent toxicities due to on- or off-target pharmacology and hybridization-independent toxicities due to non-antisense effects of the ASO. Creative Biolabs provides oligonucleotide drug toxicity assessment services for customers all over the world. Our advanced technologies and highly experienced staffs are committed to advancing your program and reducing the overall development timeline.

Oligonucleotide Drug

Oligonucleotides (ONs) have been well-studied in the past 30 years, beginning with small interfering RNAs (siRNAs), ASOs and aptamers. Most oligonucleotides therapies act through antisense mechanisms by directly targeting various RNA species, as exemplified by gapmers, steric block ONs, antagomirs, siRNAs, micro-RNA mimics, and splice switching ONs. Antisense drugs are agents that seek to target and block DNA transcription or RNA translation to moderate many disease processes. Antisense drugs consist of nucleotides linked together in short DNA or RNA sequences known as oligonucleotides. Compared with traditional drugs, oligonucleotide drugs can directly target mRNA shown in Figure 1.

The difference between ON drugs and traditional drugs. Figure 1. The difference between ON drugs and traditional Drugs.

Toxicity Assessment

There are 2 broad categories of potential toxicities: hybridization dependent toxicities and hybridization-independent toxicities.

Hybridization Independent Toxicities

  1. Proinflammatory effects

    Immunostimulatory effects have been associated with a number of siRNAs and many ASOs. The potency of the proinflammatory effects is dependent on several factors including base pair sequence and base modifications, but backbone chemistry is a major contributor.

  2. Toxicities in the liver and kidney

    These toxicities have been associated with microscopic evidence of degeneration or necrosis in the liver.

Hybridization Dependent Toxicities

Pharmacologically-based side effects result from hybridization dependent ASO binding to the desired target RNA, alternatively, to off-target RNA due to complete or partial complementarity. There are two types of hybridization dependent toxicities:

  • On-target
  • Off-target

Toxicity Assessment Services

Creative Biolabs provides two types of assessment services to assess oligonucleotide drug toxicity. These have become increasingly important in establishing the best choices for drug candidates to progress into clinical trials. They are listed below:

  • In vitro
  1. Complement fixation assays
  2. Bioinformatic genomic homology screens
  3. Hepatocyte cytotoxicity assays
  • In vivo
  1. 28-day or longer mouse hepatotoxicity/nephrotoxicity screens

Features

  • Abundant experience - our research team can efficiently operate toxicity assessments assays
  • High-throughput
  • Competitive prices
  • Fast turnaround time

Creative Biolabs' teams will work closely with partners to define specific requirements and expectations to meet the partnership objectives. Creative Biolabs aspires to become the trusted service provider of your first choice. We will continue to adapt and advance technologies and techniques in parallel to ensure success. For more information about our services, please feel free to contact us. Our advanced technologies and highly experienced staffs are committed to improving your program.

For research use only. Not intended for any clinical use.