FANA ASO Technology for RNA Targeting Therapeutics
Why use FANA ASO Technology?
Conventional RNA silencing technologies face many challenges with their use. There are many conventional technologies available to dissect and explore the wealth of genetic information now known, but many of them suffer from significant challenges. The biggest challenge is delivery, as numerous technologies are too large, negatively charged, or easily degraded to successfully enter cells and effect gene silencing on their own. They require a delivery vehicle, which can add substantial cost, toxicity, and off-target effects to the therapeutic. Off-target effects occur when the therapeutic blocks or destroys RNA that is not precisely complementary to its sequence, thus changing gene expression and protein production in an unintended, undesirable way. Further, researchers invest a lot of time in identifying the perfect RNA target for a disease or condition in the discovery phase, but then must often resort to small molecules and biologics when they translate to pre-clinical or clinical development. Many times this changes the therapeutic dynamics and ends in failure. Some of the most important desired features in any gene-silencing or loss of function studies are:
(1) Efficient knockdown or regulation of the target RNA (mRNA, miRNA, or lncRNA).
(2) Ability to bind to the target RNA in a high sequence specific manner.
(3) No toxicity.
(4) Self-delivery without an external source (e.g. without a formulation, conjugate or viral vector).
AUM Lifetech’s antisense oligonucleotides using next-generation FANA technology effectively and efficiently feature these attributes.
FANA-Antisense Oligonucleotides (FANA ASOs)
Antisense oligonucleotides offer the ability to target and silence specific sequences of RNA. These molecules consist of a short segment of DNA flanked by two segments of RNA, linked with a phosphorothioate backbone. However, they are not without their own set of challenges, and can suffer from a lack of stability and/or affinity for their target. Both of these properties can be improved by the incorporation of a modified sugar in the RNA backbone, which changes the RNA segments to a similar but more effective molecule. This next-generation molecule is called Fluoroarabinonucleic acid, or 2’ F-ANA.
FANA-ASO technology confers several key advantages over other RNA silencing technologies.
FANA-ASOs are capable of gymnotic delivery, which is self-delivery to cells without requiring a delivery agent. No formulation, conjugate, or viral vector (like AAV) is necessary. Even without a delivery vehicle, FANA-ASOs exhibit remarkable resistance to degradation by serum and cellular nucleases, which significantly extends the duration of their activity to weeks or months.
High sequence specificity:
FANA-ASOs bind to their RNA target with high affinity and specificity. They exhibit low non-specific protein binding and, unlike other technologies like siRNA, avoid RISC associated off-target effects. They likewise do not alter the biology of cells involved in the experiment, allowing for accurate analysis of gene expression and cell health.
FANA-ASOs are capable of silencing in a range of in vitro and in vivo models. Silencing can be long-term and sustained and can be achieve at low concentrations and doses. FANA ASO Technology offer high efficacy paired with high adaptability, and the ability to treat numerous gene-based diseases.
Safety: FANA ASOs are regarded as safe and do not exhibit toxicity in cellular and animal studies. FANA-ASOs are shown to have non-toxic characteristics.