Trans-complementation of E1-deleted adenovirus: a new vector to reduce the possibility of codissemination of wild-type and recombinant adenoviruses

Hum Gene Ther. 1995 Jun;6(6):711-21. doi: 10.1089/hum.1995.6.6-711.


Treatment of cystic fibrosis by gene therapy will require the development of vectors capable of efficient and safe transfer of a functional cystic fibrosis transmembrane conductance regulator (CFTR) cDNA to airway epithelia. To achieve this goal, replication-deficient (E1-) adenoviruses (Ad) are promising vectors. We have previously demonstrated efficient CFTR gene delivery to the airways of cotton rats and rhesus monkeys using a replication-deficient adenovirus, Ad-CFTR. Here, we have investigated an important safety issue, the interaction between the vector and wild-type virus which can provide the missing E1 function in trans. We show that Ad5 can mobilize the defective Ad-CFTR genome in vitro and in cotton rats. However, the extent of the complementation in vivo by wild-type virus is limited because no additional spreading or shedding of Ad-CFTR to trachea, lungs, and stools is elicited. To attenuate Ad-CFTR further, a mutation was introduced in the cis-acting regulatory sequences that control the encapsidation of the viral genome. We demonstrate that when cells are coinfected with wild-type virus and the new attenuated vector, the viral DNA containing the natural encapsidation sequences is preferentially packaged, leading to a rapid dilution of the recombinant virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adenovirus E1 Proteins / genetics*
  • Animals
  • Base Sequence
  • Cell Line
  • Cystic Fibrosis / therapy*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • DNA, Viral / genetics
  • Defective Viruses / genetics
  • Female
  • Genetic Complementation Test
  • Genetic Therapy*
  • Genetic Vectors*
  • Humans
  • Male
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Sequence Deletion
  • Sigmodontinae


  • Adenovirus E1 Proteins
  • CFTR protein, human
  • DNA, Viral
  • Oligodeoxyribonucleotides
  • Cystic Fibrosis Transmembrane Conductance Regulator