PMID- 24664760
OWN - NLM
STAT- MEDLINE
DCOM- 20140724
LR  - 20211021
IS  - 0065-2598 (Print)
IS  - 0065-2598 (Linking)
VI  - 801
DP  - 2014
TI  - Cone specific promoter for use in gene therapy of retinal degenerative diseases.
PG  - 695-701
LID - 10.1007/978-1-4614-3209-8_87 [doi]
AB  - Achromatopsia (ACHM) is caused by a progressive loss of cone photoreceptors 
      leading to color blindness and poor visual acuity. Animal studies and human 
      clinical trials have shown that gene replacement therapy with adeno-associate 
      virus (AAV) is a viable treatment option for this disease. Although there have 
      been successful attempts to optimize capsid proteins for increased specificity, 
      it is simpler to restrict expression via the use of cell type-specific promoters. 
      To target cone photoreceptors, a chimeric promoter consisting of an enhancer 
      element of interphotoreceptor retinoid-binding protein promoter and a minimal 
      sequence of the human transducin alpha-subunit promoter (IRBPe/GNAT2) was 
      created. Additionally, a synthetic transducin alpha-subunit promoter 
      (synGNAT2/GNAT2) containing conserved sequence blocks located downstream of the 
      transcriptional start was created. The strength and specificity of these 
      promoters were evaluated in murine retina by immunohistochemistry. The results 
      showed that the chimeric, (IRBPe/GNAT2) promoter is more efficient and specific 
      than the synthetic, synGNAT2/GNAT2 promoter. Additionally, IRBPe/GNAT2-mediated 
      expression was found in all cone subtypes and it was improved over existing 
      promoters currently used for gene therapy of achromatopsia.
FAU - Dyka, Frank M
AU  - Dyka FM
AD  - Department of Ophthalmology, College of Medicine, University of Florida, 1600 SW 
      Archer Rd., 32610, Gainesville, FL, USA, fmdyka@ufl.edu.
FAU - Boye, Sanford L
AU  - Boye SL
FAU - Ryals, Renee C
AU  - Ryals RC
FAU - Chiodo, Vince A
AU  - Chiodo VA
FAU - Boye, Shannon E
AU  - Boye SE
FAU - Hauswirth, William W
AU  - Hauswirth WW
LA  - eng
GR  - P30 EY021721/EY/NEI NIH HHS/United States
GR  - T32 EY007132/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Adv Exp Med Biol
JT  - Advances in experimental medicine and biology
JID - 0121103
RN  - 0 (Eye Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinol-Binding Proteins)
RN  - 0 (interstitial retinol-binding protein)
RN  - EC 3.6.5.1 (Transducin)
SB  - IM
MH  - Animals
MH  - Color Vision Defects/*genetics/pathology/*therapy
MH  - Dependovirus/genetics
MH  - Dogs
MH  - Eye Proteins/genetics
MH  - Gene Expression Regulation
MH  - Genetic Therapy/*methods
MH  - Humans
MH  - Mice
MH  - Promoter Regions, Genetic/*genetics
MH  - Rats
MH  - Recombinant Fusion Proteins/genetics
MH  - Retinal Cone Photoreceptor Cells/pathology/*physiology
MH  - Retinol-Binding Proteins/genetics
MH  - Transducin/*genetics
PMC - PMC4450355
MID - NIHMS694532
EDAT- 2014/03/26 06:00
MHDA- 2014/07/25 06:00
PMCR- 2015/06/01
CRDT- 2014/03/26 06:00
PHST- 2014/03/26 06:00 [entrez]
PHST- 2014/03/26 06:00 [pubmed]
PHST- 2014/07/25 06:00 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - 10.1007/978-1-4614-3209-8_87 [doi]
PST - ppublish
SO  - Adv Exp Med Biol. 2014;801:695-701. doi: 10.1007/978-1-4614-3209-8_87.