Engineering Drug-Like Aptamer Therapeutics

Stabilization against nuclease-mediated degradation

Conventionally, SELEX is run with diverse natural and modified nucleotide bases in the pool compositions. This greatly increases the yield of hits but not the ultimate yield of drug candidates because those aptamers typically lack metabolic stability. At Guardian we run our SELEX using only nucleotide pool compositions that are 100% stabilized against nuclease degradation, thereby ensuring that drug-like properties are baked-in to all the aptamers we discover.

Alternative routes of administration

Historically, aptamers (like monoclonal antibodies) were administered parenterally by IV infusion or SC injection. At Guardian we are exploiting the intrinsic stability of our aptamers made 100% from stabilized nucleotides against heat, light, pH, and digestive enzymes in order to achieve systemic bioavailability after oral administration and local bioavailability after topical administration (skin, eye, and GI epithelium) to open new vistas in aptamer therapeutics.

Alternative conjugation options for half-life extension

Aptamer therapeutics typically manifest short elimination half-lives after systemic administration due to rapid renal filtration, even when chemically stabilized against nuclease degradation. Typically, elimination half-life can be extended by conjugation to higher molecular weight PEG species. While suitable for some therapeutic applications, alternatives to PEG may be preferable in some circumstances. At Guardian we have successfully been able to prolong the elimination half-life of aptamers using a variety of alternatives to PEG, including long-chain fatty acids and albumin.

Aptamer-Drug Conjugates

Aptamers are well suited to serve as specific, high-affinity vectors for targeted payload delivery in Oncology. Site-specific conjugation of chemotherapeutic toxins at a defined stoichiometric ratio is readily achieved, as is incorporation of immunostimulatory CpG sequences for Immuno-Oncology applications. At Guardian, we are exploiting these properties of aptamers against a variety of cell surface-expressed cancer antigens and onco-fetal proteins

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