PMID- 17490449
OWN - NLM
STAT- MEDLINE
DCOM- 20070625
LR  - 20240109
IS  - 1467-7652 (Electronic)
IS  - 1467-7644 (Print)
IS  - 1467-7644 (Linking)
VI  - 5
IP  - 4
DP  - 2007 Jul
TI  - Field production and functional evaluation of chloroplast-derived 
      interferon-alpha2b.
PG  - 511-25
AB  - Type I interferons (IFNs) inhibit viral replication and cell growth and enhance 
      the immune response, and therefore have many clinical applications. IFN-alpha2b 
      ranks third in world market use for a biopharmaceutical, behind only insulin and 
      erythropoietin. The average annual cost of IFN-alpha2b for the treatment of 
      hepatitis C infection is $26,000, and is therefore unavailable to the majority of 
      patients in developing countries. Therefore, we expressed IFN-alpha2b in tobacco 
      chloroplasts, and transgenic lines were grown in the field after obtaining United 
      States Department of Agriculture Animal and Plant Health Inspection Service 
      (USDA-APHIS) approval. Stable, site-specific integration of transgenes into 
      chloroplast genomes and homoplasmy through several generations were confirmed. 
      IFN-alpha2b levels reached up to 20% of total soluble protein, or 3 mg per gram 
      of leaf (fresh weight). Transgenic IFN-alpha2b had similar in vitro biological 
      activity to commercially produced PEG-Introntrade mark when tested for its 
      ability to protect cells against cytopathic viral replication in the vesicular 
      stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage 
      human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating 
      properties of IFN-alpha2b were also seen in vivo. Chloroplast-derived IFN-alpha2b 
      increased the expression of major histocompatibility complex class I (MHC I) on 
      splenocytes and the total number of natural killer (NK) cells. Finally, 
      IFN-alpha2b purified from chloroplast transgenic lines (cpIFN-alpha2b) protected 
      mice from a highly metastatic tumour line. This demonstration of high levels of 
      expression of IFN-alpha2b, transgene containment and biological activity akin to 
      that of commercial preparations of IFN-alpha2b facilitated the first field 
      production of a plant-derived human blood protein, a critical step towards human 
      clinical trials and commercialization.
FAU - Arlen, Philip A
AU  - Arlen PA
AD  - Department of Molecular Biology and Microbiology, University of Central Florida, 
      Biomolecular Science, Orlando, FL 32816-2364, USA.
FAU - Falconer, Regina
AU  - Falconer R
FAU - Cherukumilli, Sri
AU  - Cherukumilli S
FAU - Cole, Amy
AU  - Cole A
FAU - Cole, Alexander M
AU  - Cole AM
FAU - Oishi, Karen K
AU  - Oishi KK
FAU - Daniell, Henry
AU  - Daniell H
LA  - eng
GR  - R01 AI052017/AI/NIAID NIH HHS/United States
GR  - R01 GM063879/GM/NIGMS NIH HHS/United States
GR  - R01 GM063879-06/GM/NIGMS NIH HHS/United States
GR  - 5R01 GM 63879-06/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070509
PL  - England
TA  - Plant Biotechnol J
JT  - Plant biotechnology journal
JID - 101201889
RN  - 0 (Interferon alpha-2)
RN  - 0 (Interferon-alpha)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Chloroplasts/*metabolism
MH  - Interferon alpha-2
MH  - Interferon-alpha/*biosynthesis/pharmacology
MH  - Plants, Genetically Modified/metabolism
MH  - Recombinant Proteins
MH  - Nicotiana/metabolism
PMC - PMC2596645
MID - NIHMS75013
EDAT- 2007/05/11 09:00
MHDA- 2007/06/26 09:00
PMCR- 2008/12/05
CRDT- 2007/05/11 09:00
PHST- 2007/05/11 09:00 [pubmed]
PHST- 2007/06/26 09:00 [medline]
PHST- 2007/05/11 09:00 [entrez]
PHST- 2008/12/05 00:00 [pmc-release]
AID - PBI258 [pii]
AID - 10.1111/j.1467-7652.2007.00258.x [doi]
PST - ppublish
SO  - Plant Biotechnol J. 2007 Jul;5(4):511-25. doi: 10.1111/j.1467-7652.2007.00258.x. 
      Epub 2007 May 9.