PMID: 8970968Dec 1, 1996Paper

Molecular characterization of replication-competent variants of adenovirus vectors and genome modifications to prevent their occurrence

Journal of Virology
K M HehirS Wadsworth

Abstract

Adenovirus (Ad) vectors for gene therapy are made replication defective by deletion of E1 region genes. For isolation, propagation, and large-scale production of such vectors, E1 functions are supplied in trans from a stable cell line. Virtually all Ad vectors used for clinical studies are produced in the 293 cell, a human embryonic kidney cell line expressing E1 functions from an integrated segment of the left end of the Ad type 5 (Ad5) genome. Replication-competent vector variants that have regained E1 sequences have been observed within populations of Ad vectors grown on 293 cells. These replication-competent variants presumably result from recombination between vector and 293 cell Ad5 sequences. We have developed Ad2-based vectors and have characterized at the molecular level examples of replication-competent variants. All such variants analyzed are Ad2-Ad5 chimeras in which the 293 cell Ad5 E1 sequences have become incorporated into the viral genome by legitimate recombination events. A map of Ad5 sequences within the 293 cell genome developed in parallel is consistent with the proposed recombination events. To provide a convenient vector production system that circumvents the generation of replication-competent variants, ...Continue Reading

References

Jul 1, 1977·The Journal of General Virology·F L GrahamR Nairn
Jan 1, 1992·Biotechnology·F L Graham, L Prevec
Oct 1, 1992·The Journal of Experimental Medicine·R E DonahueR Moen
May 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·H S GinsbergG A Prince

❮ Previous
Next ❯

Citations

Dec 2, 1999·The Journal of General Virology·P S ReddyS K Tikoo
Mar 8, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·L MohrJ R Wands
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·D C WhiteW J Koch
Oct 20, 2000·The Journal of General Virology·W C Russell
May 25, 2002·The Journal of General Virology·Hendrik J RademakerRob C Hoeben
Dec 23, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Claire SoudaisEric J Kremer
Oct 31, 2008·Current Protocols in Neuroscience·Thomas SouthgateMaria G Castro
Aug 1, 2010·Viruses·Imre Kovesdi, Susan J Hedley
Mar 31, 2000·Nature Medicine·G ThurstonG D Yancopoulos
Jun 28, 2001·Human Gene Therapy·M HillgenbergM Strauss
Apr 23, 2008·Current Protocols in Neuroscience·T D SouthgateM G Castro
May 23, 2006·Pharmacological Reviews·Ajit S Narang, Ram I Mahato
Mar 7, 2014·Human Gene Therapy·Jort VellingaMenzo Havenga
Oct 3, 1999·Gene Therapy·F J FallauxR C Hoeben
Mar 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·G P LinetteF G Haluska
May 12, 2004·Biotechnology and Bioengineering·Inn H Y YukSean P Forestell
Jan 17, 2008·The Journal of General Virology·Alexander N LukashevRichard D Iggo
Jul 11, 2014·Journal of Virology·Ryann C GuayasaminMichael D Robek
Jul 28, 2015·Biotechnology Journal·Ana F RodriguesAna S Coroadinha

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.