Conditionally controlled, attenuated HIV vaccine
US6541003B1 · kind B1 · utility
Assignee
Inventor
Key dates
| Filing date | Jul 25, 2000 |
| Grant date | Apr 1, 2003 |
| Priority date | — |
| Expiry date | Aug 19, 2020 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC12N2830/003
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
A live attenuated human immunodeficiency virus type 1 (HIV-1) whose replication is not constitutive but is instead conditionally regulated (such that rounds of reverse transcription with accompanying potential for error are strictly limited) might yield a paradigm that minimizes evolution to virulence and facilitate vaccine development. We have broached the concept of conditional control of HIV-1 through gain-of-function. Here, we describe the design of constitutively inactive HIV-1 genomes (HIV-DoxT and HIV-DoxSp) which can be conditionally resuscitated to an active state by tetracycline or related analogues. The HIV-DoxT construct comprises an inactivating mutation engineered into TAR, thereby rendering the virus non-responsive to Tat, a 302-bp DNA fragment (TetopT) which contains the tet-operator ligated into a position upstream of the HIV TATAA box, in both the 5′ and 3′ LTRs, and a reverse tetracycline-controlled activator (RTTA) coding sequence in place of the nef coding region. The HIV-DoxSp construct contains three additional Sp1 sites in the TetopT promoter upstream of the TATAA box thereby generating the promoter TetopSp. Genotypically, HIVDoxT is tat(+)tar(&#…
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.