Antisense Oligonucleotide (ASO) Delivery Services
Introduction
In order to achieve higher specificity and to maximize the gene silencing function of Anti-sense Oligonucleotides (ASO), ASO needs to be delivered to the target tissue. ASOs are usually large hydrophilic polyanions, which are not easy to cross the plasma membrane and are easily cleared in vivo. Creative Biolabs can provide reasonable, customized, and efficient ASO delivery solutions for customers to choose from, including a series of additional services such as efficiency testing.
ASO Delivery System
GalNAc Conjugates
GalNAc is a carbohydrate fragment bound to ASPGR. ASPGR is highly expressed in the liver, so it can deliver ASO drugs to the liver with high efficiency and specificity. During endosomal acidification, GalNAc fragments are degraded by enzymes, resulting in the release of oligonucleotides1.
Aptamer Conjugates
Aptamers can be considered "chemical antibodies", which bind to their respective target proteins with high affinity, simple manufacture, low cost, small size, and low immunogenicity.
Peptide conjugates
Peptides that can target ASO to tissue or cells. CPPs are short amphotic or cationic peptide fragments that can be chemically coupled directly to charge-neutral ASO to exert antibacterial and antiviral effects.
Lipid Nanoparticles
LNPs contain four basic components: cationic or ionized lipids, cholesterol, helper lipids, and polyethylene glycol (PEG) lipids. After polyanionic nucleic acid drugs are mixed with lipids, nucleic acids aggregate to trigger endocytogenic uptake of nanoparticles suitable for delivery to organs/tissues with abundant capillary systems2.
Fig.1 Components of LNPs.2
Exosome
Exosomes are lipid bilayer-coated vesicles with a diameter of about 100nm, capable of crossing biofilms, immune phagocytosis, long cycle, non-toxic, and some also have pro-regeneration and anti-inflammatory properties that can enhance the effect of ASO delivery.
Fig.2 Process of small nucleic acid drug delivery by exosomes.3
Spherical Nucleic Acid
SNA particles are composed of hydrophobic core nanoparticles whose surface hydrophilic ASO is densely packed on the surface via mercaptan bonds and has the potential to cross the blood-brain barrier and is also used for local delivery to skin keratinocytes.
Fig.3 Two basic structures of SNA.Distributed under CC BY-SA 3.0, from Wiki, without modification.
DNA nanostructures
Tetrahedral DNA nanoparticles for nucleic acid delivery, which are designed to contain nucleic acid drugs, are small and do not accumulate in the liver and can be delivered to other tissues, but may result in low bioavailability due to their small size.
Fig.4 Tetrahedral structure of DNA nanostructures.Distributed under CC BY-SA 3.0, from Wiki, without modification.
Highlights
Creative Biolabs offers a variety of delivery options based on years of experience, and our scientists provide ASO with high-quality delivery system development services to meet the customer's individual needs as best as possible. Our strengths include:
- The delivery method can be selected according to the size and chemistry of the ASO
Creative Biolabs has advanced ASO delivery technology, including but not limited to GalNAc, LNPs, cationic polymers, etc., to achieve efficient and accurate delivery of different types of oligonucleotide drugs and to various target tissues.
- High-quality research and development services
Creative Biolabs has a research and development laboratory in line with international standards and advanced instruments and equipment, which can provide customers with one-stop services from delivery to efficiency evaluation.
- Strict quality control
In the development process, strict quality control standards are followed to ensure the accuracy and reliability of every step of the operation. Through perfect detection means and data analysis, the purity, stability, and biological activity of drugs are comprehensively evaluated to ensure the quality and safety of drugs.
- Excellent after-sales service
Establish an efficient after-sales service response mechanism, timely understand customer needs and satisfaction, and improve service deficiencies.
Related Services
References
- Springer, Aaron D., and Steven F. Dowdy. "GalNAc-siRNA conjugates: leading the way for delivery of RNAi therapeutics." Nucleic acid therapeutics 28.3 (2018): 109-118.
- Raguram, Aditya, Samagya Banskota, and David R. Liu. "Therapeutic in vivo delivery of gene editing agents." Cell 185.15 (2022): 2806-2827. Distributed under Open Access license CC BY 4.0. The image was without modification
- Song, Hang, et al. "Exosome-based delivery of natural products in cancer therapy." Frontiers in cell and developmental biology 9 (2021): 650426. Distributed Under Open Access license CC BY 4.0. The image was modified by extracting and using only Part A of the original image.
