Caged DNA does not aggregate in high ionic strength solutions.
The assembly of DNA into compact particles that do not aggregate in physiologic salt solution occurs naturally in chromatin and viral particles but has been challenging to duplicate using artificial constructs. Cross-linking amino-containing polycations in the presence of DNA with bisimidoester cross-linker leads to the formation of caged DNA particles that are stable in salt solutions. This first demonstration of caged DNA provides insight into how natural condensation processes avoid aggregation and a promising avenue for developing nonviral gene therapy vectors.
Mirus Corporation, 545 Science Drive, Madison, Wisconsin 53711, USA. vladimirt@genetransfer.com
V S
VS
Trubetskoy
A
A
Loomis
P M
PM
Slattum
J E
JE
Hagstrom
V G
VG
Budker
J A
JA
Wolff
D003432:Cross-Linking Reagents; D003510:Cyclohexanes / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D007202:Indicators and Reagents; D008854:Microscopy, Electron; D009994:Osmolar Concentration; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D011073:Polyamines / Q000737:chemistry; D012996:Solutions; D014162:Transfection; D014461:Ultracentrifugation
D003432:Cross-Linking Reagents; D003510:Cyclohexanes; D007202:Indicators and Reagents; D011073:Polyamines; D012996:Solutions; C067220:di-tert-butylperoxy-3,3,5-trimethylcyclohexane peroxide; D004247:DNA