PMID- 16454658
OWN - NLM
STAT- MEDLINE
DCOM- 20060310
LR  - 20121115
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 17
IP  - 2
DP  - 2006 Feb
TI  - A simplified approach to improve the efficiency and safety of ex vivo 
      hematopoietic gene therapy in fanconi anemia patients.
PG  - 245-50
AB  - Fanconi anemia (FA) is an inherited DNA repair disorder characterized by genetic 
      instability of cells lacking a functional FA/BRCA pathway. Previous studies have 
      shown that in vitro stimulation of bone marrow cells (BMCs) from FA mice promotes 
      apoptosis, reduces the reconstitution ability of the stem cells, and induces 
      myelodysplasia and myeloid leukemia upon reinfusion of the cells. This suggests 
      the convenience of adapting standard protocols of gene therapy to FA. Here we 
      show that the reserve of BM progenitors in FA patients is generally below 20% of 
      normal values. Because this reduced reserve could activate the cycling of BM 
      progenitors, we developed a simplified protocol to transduce BMCs from FA 
      patients with gammaretroviral vectors. We demonstrate that a short in vitro 
      manipulation (12-24 hr) of fresh mononuclear BMCs is sufficient to transduce 42% 
      of hematopoietic progenitors from FA-A patients, in the absence of in vitro 
      prestimulation. When FANCA-expressing vectors were used, this simple procedure 
      reversed the phenotype of the BM progenitors from these patients. We propose that 
      our approach will be more efficient and safer compared with standard gene therapy 
      protocols for FA.
FAU - Jacome, A
AU  - Jacome A
AD  - Spanish Fanconi Anemia Research Network, Madrid 28040, Spain.
FAU - Navarro, S
AU  - Navarro S
FAU - Casado, J A
AU  - Casado JA
FAU - Rio, P
AU  - Rio P
FAU - Madero, L
AU  - Madero L
FAU - Estella, J
AU  - Estella J
FAU - Sevilla, J
AU  - Sevilla J
FAU - Badell, I
AU  - Badell I
FAU - Ortega, J J
AU  - Ortega JJ
FAU - Olive, T
AU  - Olive T
FAU - Hanenberg, H
AU  - Hanenberg H
FAU - Segovia, J C
AU  - Segovia JC
FAU - Bueren, J A
AU  - Bueren JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
SB  - IM
MH  - Bone Marrow Cells/physiology
MH  - Cells, Cultured
MH  - Fanconi Anemia/blood/*therapy
MH  - Gammaretrovirus/genetics
MH  - Genetic Therapy/adverse effects/*methods
MH  - Hematopoietic Stem Cells/*physiology
MH  - Humans
MH  - Reference Values
MH  - Transduction, Genetic/*methods
EDAT- 2006/02/04 09:00
MHDA- 2006/03/11 09:00
CRDT- 2006/02/04 09:00
PHST- 2006/02/04 09:00 [pubmed]
PHST- 2006/03/11 09:00 [medline]
PHST- 2006/02/04 09:00 [entrez]
AID - 10.1089/hum.2006.17.245 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2006 Feb;17(2):245-50. doi: 10.1089/hum.2006.17.245.