Interferon is used as a treatment for hepatitis B but because it is a very small protein it is quickly filtered from the blood by the kidneys. Researchers at Technische Universitaet Muenchen, Germany believe they can overcome this problem and have spun out a company.
The new company, XL-protein, will develop the technology that couples interferon with a synthetic PEG (polyethylene glycol) molecule. PEG absorbs water and swells up, resulting in interferon being attached to something that is unable to pass through the pores in the kidneys.
However, PEG could accumulate in the body and consequently the researchers used genetic engineering to create an amino acid string with similar swelling properties but that also breaks down or is discharged over an extended period of time.
Consequently the half-life of the therapeutic is increased, by a factor of 60 in first trials in animals, and the dosing schedule can be altered to be more convenient for the patient.
Lowering production costs
The researchers created the synthetic PEG from proline, alanine and serine (PAS) and, because interferon also consists of amino acids, the PASylated form can “be easily generated”.
This is achieved by joining the DNA segments that code for the PAS amino acid sequence and the interferon and inserting this into bacteria.
Following insertion the bacteria produce the PASylated interferon in one piece, reducing the number of production steps compared to chemically coupled PEG. Arne Skerra, who helped develop the technique, believes “this will lead to a significant drop in production cost”.
The researchers believe there could be a “huge market” for the technology because it can potentially apply to all small proteins, such as growth factors or functional antibody fragments.