ADI-PEG 20 (antiviral)

ADI-PEG 20 is arginine deiminase (ADI) formulated with polyethylene glycol having an average molecular weight of 20 kilodaltons (PEG 20). It is a novel protein therapeutic that has demonstrated antiviral activity against hepatitis C virus. Administered by intramuscular injection, it catabolizes circulating arginine to yield citrulline and ammonia.

Urea Cycle

ADI is a microbial enzyme that degrades arginine, an amino acid that has been demonstrated to be required for viral replication in vitro. While host cells are able to synthesize arginine from metabolic precursors via the urea cycle (see left image), some viruses such as certain adenoviruses (Rouse, Bonifas & Schlesinger, 1963; Russell & Becket, 1968; Dubes et al. I969), herpes simplex virus (Tankersley, I964), SV40 virus (Goldblum, Ravid & Becker 1968), cytomegalovirus (Minamishima & Benyesh-Melnick, I969) and polyoma virus (Winters & Consigli, I969) have been shown to have an essential requirement for arginine. Therefore, depleting arginine from the blood may limit viral growth.

ADI is formulated with polyethylene glycol (PEG) of 20,000 dalton molecular weight to prolong the circulating half life and decrease antigenicity of ADI. Similar pegylation technology has been used with microbially-derived therapeutic proteins for systemic delivery of anticancer drugs.

The formulation with PEG also allows for the drug to be administered by intramuscular (i.m.) injection which avoids possible complications known to be associated with multiple intravenous administrations. Furthermore, i.m. injections can readily be administered in an outpatient hospital setting, in a physician's office or even in a patient's home.