I am trying to prepare hyaluronic acid - PEG hydrogels to which DNA (1200bp) is covalently coupld by copper-free azid click chemistry. Prior to gelation, initial precursor mixture including DNA, PEG, and hyaluronic acid shows no DNA aggregation in 15 mM Phosphate buffer (pH 6.5). However, within gelation process stepwise DNA aggregation is observed. I guessed that this might be affected by the polyanionic nature of hyaluronic acid, which is why I added 300 mM NaCl to buffer solution giving even more aggregates. Is there any chance to avoid this aggregation or does anyone know by which this phenomenon is affected ?
As a chemist I am not an expert in the field of DNA-conjugation and hope one can help me out! Thanks !