TY - JOUR
T1 - Liver-directed gene therapy
T2 - Promises, problems and prospects at the turn of the century
AU - Ghosh, Siddhartha S.
AU - Takahashi, Masahiko
AU - Thummala, Narsing R.
AU - Parashar, Bhupesh
AU - Chowdhury, Namita Roy
AU - Chowdhury, Jayanta Roy
N1 - Funding Information:
This work was supported in part by the following NIH grants: ROI-DK 46057 (to J.R.C.); ROl-DK 39137 (to N.R.C.), P30-DK 41296 (Liver Research Core Center).
PY - 2000
Y1 - 2000
N2 - Although liver-directed gene therapy arrived later than gene therapy directed at bone marrow cells, intrinsic advantages of the liver as a target organ make it likely that gene therapy for liver diseases will be among the first therapeutically relevant applications of this treatment modality at the onset of the 21st century. Vectorology for gene transfer to the liver is advancing rapidly, and it is safe to predict that gene therapy vehicles that will be in clinical use a decade from now, have not yet been developed. None of the currently available modes of gene transfer to the liver is optimal for all types of applications. Nonetheless, the concerted effort of many investigators has provided a wide choice of non-viral and viral vectors for gene transfer to the liver for use in specific situations. Original strategies for liver-directed gene therapy included substitution of missing gene products, overexpression of intrinsic or extrinsic genes and inhibition of expression of specific genes. To the list is now added the possibility of site-specific correction or generation of mutations within specific genes in somatic cells of living adult animals. Thus, despite some initial faux pas, liver-directed gene therapy is poised to make an important impact on health care in the year 2000 and beyond.
AB - Although liver-directed gene therapy arrived later than gene therapy directed at bone marrow cells, intrinsic advantages of the liver as a target organ make it likely that gene therapy for liver diseases will be among the first therapeutically relevant applications of this treatment modality at the onset of the 21st century. Vectorology for gene transfer to the liver is advancing rapidly, and it is safe to predict that gene therapy vehicles that will be in clinical use a decade from now, have not yet been developed. None of the currently available modes of gene transfer to the liver is optimal for all types of applications. Nonetheless, the concerted effort of many investigators has provided a wide choice of non-viral and viral vectors for gene transfer to the liver for use in specific situations. Original strategies for liver-directed gene therapy included substitution of missing gene products, overexpression of intrinsic or extrinsic genes and inhibition of expression of specific genes. To the list is now added the possibility of site-specific correction or generation of mutations within specific genes in somatic cells of living adult animals. Thus, despite some initial faux pas, liver-directed gene therapy is poised to make an important impact on health care in the year 2000 and beyond.
KW - Gene therapy
KW - Liver diseases
KW - Site-directed gene repair
KW - Vectors, viral, non-viral
UR - http://www.scopus.com/inward/record.url?scp=0034006838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034006838&partnerID=8YFLogxK
U2 - 10.1016/S0168-8278(00)80429-8
DO - 10.1016/S0168-8278(00)80429-8
M3 - Article
C2 - 10728808
AN - SCOPUS:0034006838
SN - 0168-8278
VL - 32
SP - 238
EP - 252
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - SUPPL.1
ER -