Poster Presentation 2014 International Biophysics Congress

The emptied bacteriophage T4 capsid: A novel nanoparticle vehicle to efficiently deliver genes into the body (#382)

Guofen Gao 1 2 , Marthandan Mahalingam 2 , Pan Tao 2 , Zhihong Zhang 2 , Yan-Zhong Chang 1 , Venigalla B. Rao 2
  1. Hebei Normal University, Shijiazhuang, Hebei, China
  2. The Catholic University of America, Washington, DC, USA

As the modern biological and medical research going deeper, the current gene delivery techniques start to show insufficient safety and/or efficiency, and new technologies are of crucial need. The 120 x 86 nm capsid of bacteriophage T4 is an ideal material for developing into a good gene delivery nanoparticle, as it can be engineered both inside and outside. The empty capsid can be filled with foreign DNA molecules under in vitro conditions and protect the DNA from nuclease degradation; the capsid surface can be arrayed with foreign proteins as fusions to the outer capsid proteins, Hoc and Soc, to endow the delivery particle with targeting property or cell-membrane penetrating ability. This T4 phage gene delivery particle has been applied to the development of HIV-1 DNA vaccine. The HIV-1 genes of envelope proteins gp41, gp145 and gp160 were packaged inside the capsid, and the surface was arrayed with antigens and dendritic cell targeting ligands, including gp41 and gp145 as fusions of Soc, and Dec205 mAb as fusions of Hoc. The T4 nanoparticle delivered DNA vaccines elicited robust titers of neutralization antibodies to the epitopes in the membrane proximal external region of gp41. As a comparison, the group vaccinated with only the protein antigens did not show as high titers of neutralization antibodies. These results indicated that the T4 nanopariticle efficiently delivered DNA into the body, and the delivered genes were abundantly expressed with their natural conformations retained. Using T4 nanoparticle as a novel gene delivery technology may achieve highly efficient in vivo DNA delivery with good safety. Research, utilizing this novel T4 nanoparticle gene delivery technology, on the mechanism and treatment of neurodegenerative diseases is also in progress.