Biopolym. Cell. 1990; 6(1):51-56.
DNA diagnostics and approaches to gene therapy of hereditary α1-antitrypsin deficiency
1Schwartzman A. L., 1Strakhova M. P., 1Gaitskhoki V. S., 2Berger W., 2Coutelle Ch.
  1. Institute of Experimental Medicine, Academy of Medical Sciences of the USSR
    Leningrad, USSR
  2. Central Institute for Molecular Biology, Academy of Sciences of DDR
    Berlin-Buch, DDR


The recombinant clones synthesizing immunoreactive α1-antitrypsin were isolated from expression library of human liver cDNA. Their sequencing has shown that they contain AT cDNAs lacking 20–100 codons from 5'terminal region of AT cRNA. These clones were used as probes for the diagnosis of inherited AT deficiency based on linked Maelll polymorphism. cDNA clones including all the codons for mature AT starting from +2 codon are obtained to construct bacterial strains-producents of AT as well as of recombinant DNAs necessary for gene therapy of AT deficiency.


[1] Carrell RW, Jeppsson JO, Laurell CB, Brennan SO, Owen MC, Vaughan L, Boswell DR. Structure and variation of human alpha 1-antitrypsin. Nature. 1982;298(5872):329-34.
[2] Long GL, Chandra T, Woo SL, Davie EW, Kurachi K. Complete sequence of the cDNA for human alpha 1-antitrypsin and the gene for the S variant. Biochemistry. 1984;23(21):4828-37.
[3] Cox DW, Johnson AM, Fagerhol MK. Report of Nomenclature Meeting for alpha 1-antitrypsin, INSERM, Rouen/Bois-Guillaume-1978. Hum Genet. 1980;53(3):429-33.
[4] Jeppsson JO, Laurell CB. The amino acid substitutions of human alpha 1-antitrypsin M3, X and Z. FEBS Lett. 1988;231(2):327-30.
[5] Riley JH, Bathurst IC, Edbrooke MR, Carrell RW, Craig RK. Alpha 1-antitrypsin and serum albumin mRNA accumulation in normal, acute phase and ZZ human liver. FEBS Lett. 1985;189(2):361-6.
[6] Nukiwa T, Satoh K, Brantly ML, Ogushi F, Fells GA, Courtney M, Crystal RG. Identification of a second mutation in the protein-coding sequence of the Z type alpha 1-antitrypsin gene. J Biol Chem. 1986;261(34):15989-94.
[7] Cox DW, Billingsley GD. Restriction enzyme MaeIII for prenatal diagnosis of alpha 1-antitrypsin deficiency. Lancet. 1986;2(8509):741-2.
[8] Fagerhol MK, Laurell CB. The Pi system-inherited variants of serum alpha 1-antitrypsin. Prog Med Genet. 1970;7:96-111. Review.
[9] Kidd VJ, Wallace RB, Itakura K, Woo SL. alpha 1-antitrypsin deficiency detection by direct analysis of the mutation in the gene. Nature. 1983 Jul 21-27;304(5923):230-4.
[10] Ross Boswell D, Carrell R. О±1-Antitrypsin: Molecules and medicine. Trends Biochem Sci. 1986;11(3):102-3.
[11] Ledley FD, Grenett HE, Bartos DP, Woo SL. Retroviral mediated transfer and expression of human alpha 1-antitrypsin in cultured cells. Gene. 1987;61(1):113-8.
[12] Perlino E, Cortese R, Ciliberto G. The human alpha 1-antitrypsin gene is transcribed from two different promoters in macrophages and hepatocytes. EMBO J. 1987;6(9):2767-71.
[13] Young RA, Davis RW. Yeast RNA polymerase II genes: isolation with antibody probes. Science. 1983;222(4625):778-82.
[14] Maniatis T, Fritsch EF, Sambrook J. Molecular cloning - a laboratory manual. New York, Cold Spring Harbor, 1982; 545 p.
[15] Berger W, Schwarzman A, Coutelle C, Neifakh S. Der alpha-l-antitrypsin-mangel-isolation von alpha-1-antitrypsin cDNA gensonden aus einer efprimierenden-gt11 humanlebergenbank. Z Klin Med. 1988; 43(3):583-6.