Physical Characterization and Stabilization of a Lentiviral Vector Against Adsorption and Freeze-Thaw

Journal of Pharmaceutical Sciences
Ozan S KumruDavid B Volkin

Abstract

A replication-deficient lentiviral vector encoding the tumor antigen gene NY-ESO-1 was characterized in terms of vector morphology, particle size range, concentration, and zeta potential using a variety of physical methods. Environmentally stressed vector samples were then evaluated in terms of viral vector particle size and concentration by nanoparticle tracking analysis (NTA). These NTA stability results correlated reasonably well with a quantitative polymerase chain reaction assay for quantitation of viral genome copy number (r2 = 0.80). Approximately 40 pharmaceutical excipients were examined for their ability to stabilize the vector against exposure to an adsorptive container surface (glass) as well as freeze-thaw cycling using NTA as the screening method. Stabilizing additives that inhibited viral vector particle loss under these conditions included proline, lactose, and mannitol. Several candidate frozen liquid formulations that contained a combination of these lead excipients and various buffering agents were further evaluated for their ability to stabilize the viral vector. The additional benefit of lowering the Tris buffer concentration was observed. This study highlights the use of physical particle assays such as NT...Continue Reading

References

May 1, 1979·The Journal of General Virology·M K EstesC P Gerba
Jun 1, 1991·Trends in Biotechnology·M Wahlgren, T Arnebrant
May 1, 1974·Journal of Virology·J S PierceJ H Strauss
Nov 1, 1983·Analytical Biochemistry·C H Suelter, M DeLuca
Aug 1, 1996·Journal of Pharmaceutical Sciences·S LiR T Borchardt
Apr 26, 2000·Haemophilia : the Official Journal of the World Federation of Hemophilia·A G McLeodC P Hayward
Nov 29, 2002·Gene Therapy·J B Connolly
Sep 7, 2004·Journal of Pharmaceutical Sciences·Robert K EvansDavid B Volkin
Jun 2, 2005·Journal of Pharmaceutical Sciences·Li ShiDavid B Volkin
Dec 6, 2005·Journal of Virological Methods·María de las Mercedes SeguraAmine Kamen
Dec 24, 2005·Journal of Pharmaceutical Sciences·Jason RexroadC Russell Middaugh
Jul 25, 2006·Advances in Cancer Research·Sacha GnjaticLloyd J Old
Aug 11, 2006·Proceedings of the National Academy of Sciences of the United States of America·Zoya Ignatova, Lila M Gierasch
Jan 17, 2007·Nature Reviews. Microbiology·Laurent BalvayThéophile Ohlmann
Jun 19, 2007·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Andrea Hawe, Wolfgang Friess
Jul 4, 2007·Nature Reviews. Genetics·Reinhard WaehlerDavid T Curiel
Sep 18, 2007·Molecular Biotechnology·Adam S Cockrell, Tal Kafri
Oct 30, 2007·Methods in Cell Biology·Daniel Harries, Jörg Rösgen
Apr 3, 2008·Human Vaccines·Julian KissmannC Russell Middaugh
Jun 10, 2009·The Journal of Gene Medicine·Marlene CarmoPedro Estilita Cruz
Oct 30, 2010·Immunity·Margaret A Liu
Dec 16, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Boris KantorTal Kafri
Mar 23, 2011·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Johannes Mathes, Wolfgang Friess
Apr 28, 2011·Journal of Pharmaceutical Sciences·Jared S BeeMariana N Dimitrova
May 24, 2011·Analytical Chemistry·Gleb G MironovMaxim V Berezovski
Jan 15, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Semih U TareenScott H Robbins
May 29, 2014·Expert Review of Vaccines·Umit Kartoglu, Julie Milstien
Jul 6, 2014·Biologicals : Journal of the International Association of Biological Standardization·Ozan S KumruDavid B Volkin
Jul 8, 2014·Virology·Susanne Heider, Christoph Metzner
Nov 5, 2014·Journal of Pharmaceutical Sciences·Ozan S KumruC Russell Middaugh
Sep 15, 2015·Vaccine·L J J HansenT R M De Beer
Oct 9, 2015·AIMS Biophysics·Wei ZhangLouis M Mansky
Nov 7, 2015·PloS One·Nikolai NikitinOlga Karpova
Mar 5, 2016·Molecular Therapy. Methods & Clinical Development·Michele E MurphyBrenna Kelley-Clarke
Apr 26, 2016·Molecular Therapy. Methods & Clinical Development·Otto-Wilhelm MertenChiara Bovolenta

❮ Previous
Next ❯

Citations

Oct 8, 2020·Biomaterials Science·Kübra Kaygisiz, Christopher V Synatschke
Oct 23, 2020·Biotechnology Journal·Ana Sofia MoreiraCristina Peixoto
Nov 27, 2020·Journal of Pharmaceutical Sciences·Daan J A CrommelinWim Jiskoot
Feb 13, 2021·Viruses·Christopher Perry, Andrea C M E Rayat
May 29, 2021·RSC Medicinal Chemistry·Lewis L BrayshawChristopher Herring
Apr 30, 2020·Molecular Therapy. Methods & Clinical Development·Anniina J ValkamaHanna P Lesch

❮ 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.