1. Field of the Invention
The present invention relates to a nucleic acid adsorbent; methods for adsorbing, removing, dissociating, and recovering nucleic acids using the same; and a method for regenerating the same.
2. Description of the Related Art
In recent years, with the increasing development of drugs using biotechnology, useful biologically important substances have been mass-produced by recombinant genes. Drugs produced using recombinant gene technology often contain nucleic acids as impurities. The influence of such nucleic acids on the living body has not been fully clarified. For this reason, FDA and WHO have published guidelines on residual nucleic acids in biologicals. According to the guideline of WHO, it is desirable that the amount of residual nucleic acids in an adult dose should be not more than 10 ng (WEEKLY EPIDEMIOLOGICAL RECORD, No. 20, 16, MAY, 1997).
Methods for removing nucleic acids have been known: One example is the technique of eliminating nucleic acids by aggregation and precipitation using a water-soluble nucleic acid adsorbent. The nucleic acid adsorbent is protamine sulfuric acid or streptomycin (“Biochemical Experiment Lecture 5,” p. 201, edited by the Japanese Biochemical Society, published by Tokyo Kagaku Dojin). Another nucleic acid adsorbent is cationic hydroxyalkylcellulose (Japanese Laid-Open Application No. 1989-25791). However, this method requires, when aggregation treatment is performed on the water-soluble adsorbent, the operations of removing aggregates by centrifugation and then removing a soluble flocculating agent that has been added in excess.
The chromatography techniques, such as ion exchange, gel filtration, and affinity chromatography, have also been considered. These techniques have several problems, such as a low nucleic acid removal rate, a low removal of the target biological substance, complicated setting of removal conditions, inadequate mechanical strength of chromatography agents, none of which are preferred for industrial use. For example, in the method for removing nucleic acids by adsorption with chitosan, when the pH of the solution containing nucleic acids is basic, the ability to remove nucleic acids is reduced (Japanese Laid-Open Application No. 1991-109397 and Japanese Laid-Open Application No. 1991-109940).
USPTO Backgrounds
USPTO Backgrounds