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T*
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T*
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T*
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T*
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T*
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T*
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T*
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T*
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T*
[(t)11(h)12.4(e)-172(s)13.6(o)12.2(c)0(i)21.9(a)0(l)24(,)-174.2(l)13.9(e)12.2(ga)25.3(l,)-165.7(a)15.5(n)12.4(d)-175.9(c)13.4(u)12.4(l)0(t)25(u)12.4(ra)23.5(l)-175.8(l)13.9(e)12.2(v)0(e)22.1(l)-170.3(if)-162.5(it)-164.7(w)16.8(a)0(s)-160.6(t)11(o)-172(b)0(e)22.3(c)13.4(o)12.2(m)12.4(e)]TJ
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0 -1.1923 TD
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[(b)-12.6(i)11.4(rths)-12.6(.)-184.1(P)-2.4(rena)-12.6(t)8.5(a)2.9(l)-193.8(d)-12.6(i)9.7(a)-12.6(g)12.7(n)-.2(os)-12.6(i)9.5(s)-194.1(wa)-12.6(s)-184.1(n)-.2(ot)-196.7(an)-195.3(opti)-12.6(o)8.1(n)-195.3(in)-195.3(those)]TJ
T*
-.0128 Tc
[(da)-12.8(y)7.1(s).8(,)-219.6(s).8(o)-217.3(t)-1.8(he)-217.4(resul)-12.8(t)-210(o)4.9(f)-221.8(scr)-12.8(e)7.5(ening)-219.7(a)2.7(nd)-221.2(couns)-12.8(e)13(l)-12.8(i)9.6(n)-.4(g)-219.7(c).6(oul)-12.8(d)]TJ
0 -1.1869 TD
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0 -1.1923 TD
[(would)-483.6(predictably)-482.3(meet)-477.7(with)-482.3(resistance)-481(even)-484.3(by)]TJ
T*
.0143 Tc
[(at-risk)-411.6(c).6(ouples,)-414.7(a)2.7(nd)-410.9(the)-412.5(p)1(eople)-412.5(had)-416.3(t)3.7(o)-412.5(b)2.7(e)-412.5(a)-2.8(sked)]TJ
0 -1.1869 TD
0 Tc
[(whether)-207.4(such)-202.8(a)-206.7(program)-207.4(would)-207.2(be)-205.3(acceptable.)-205.7(Such)]TJ
0 -1.1923 TD
[(an)-476.1(enquiry)-473.8(was)-469(not)-473.7(undertaken)-473(until)-478.2(the)-473.7(1960s)]TJ
T*
[(when)-249.6(George)-248.3(Stamatoyannopou)7(los)-252.9(stepped)-250.9(in.)]TJ
1.1435 -1.1869 TD
[(He)-298.3(chose)-299.2(a)-304.3(village)-301(in)-298.8(Greece)-298.9(in)-304.3(the)-300.3(Arta)-298.9(region,)]TJ
-1.1435 -1.1923 TD
[(known)-312.3(to)-312.7(have)-307.7(a)-315.1(high)-309(carrier)-316.5(rate)-310.9(for)-313.4(beta)-308.9(thalas-)]TJ
T*
[(semia,)-215(where)-214.6(he)-219.2(rst)-215.1(went)-218.4(to)-215.2(screen)-220.7(the)-213.6(population)]TJ
0 -1.1869 TD
[(and)-413.6(to)-410.3(counsel)-413.7(them)-407.1(concerning)-416.1(the)-408.7(risk)-417.4(of)-408.1(mar-)]TJ
0 -1.1923 TD
[(riage)-292.7(between)-286.9(carriers.)-292.9(He)-292.9(suggested)-286.9(avoidance)-293(of)]TJ
T*
[(such)-208.3(marriages)-205.3(and)-207.6(returned)-213.3(a)-206.7(year)-203.7(later)-210.3(to)-209.8(see)-205.8(the)]TJ
0 -1.1869 TD
[(result.)-677.5(He)-672.2(noted)-675.3(that)-670.8(there)-675.7(was)-674.9(no)-674.5(marriage)]TJ
0 -1.1923 TD
[(avoidance)-184.6(on)-181.3(the)-186.5(basis)-182.7(of)-185.9(genetic)-185.8(risk.)-185.2(These)-183.1(results)]TJ
T*
[(were)-281.3(published)-279.5(in)-277.2(1974)-279.6(in)]TJ
/F8 1 Tf
12.1887 0 TD
[(Exerpta)-281.2(Medica)]TJ
/F4 1 Tf
7.2514 0 TD
(.)Tj
-18.2966 -1.1869 TD
[(His)-272.2(next)-274.2(stop)-274.5(was)-273.9(Cyprus)-275.7(in)-277.2(1972,)-269.6(another)-273.8(high)]TJ
-1.1435 -1.1923 TD
[(prevalence)-266.6(area.)-264(In)-264.4(the)-267.8(early)-265.7(1970s,)-261.4(the)-267.8(treatment)]TJ
T*
[(of)-456.9(thalassemia)-452(was)-452.7(accepted)-452.8(to)-453.6(be)-454.6(regular)-456.6(blood)]TJ
0 -1.1869 TD
[(transfusion)-506.5(and)-505.7(iron)-506.2(chelation)-500.7(using)-506.8(desferriox-)]TJ
0 -1.1923 TD
[(amine.)-313.7(The)-317.4(dose)-311.3(of)-316(the)-316.6(drug)-319(was)-311.8(not)-316.6(well)-311.6(dened,)]TJ
T*
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[(and)-469.8(t)-1(he)-465.9(government)-467.1(was)-470(p)-3.7(roviding)-468.3(12)-468.1(\(500)-164.6(mg\))]TJ
0 -1.1869 TD
0 Tc
[(vi)18.4(al)18.5(s)-457.9(p)0(e)20.6(r)-463.5(m)12.4(o)0(n)19.2(t)11(h)-464.5(t)11(o)-459.3(e)12.2(ac)18.1(h)-459.1(p)0(a)18.4(t)11(ie)15.3(n)12.4(t)11(.)-461.5(I)0(t)-450.1(w)11.4(as)-453.3(h)12.4(o)0(w)18.2(e)12.2(ve)16.7(r)]TJ
0 -1.1923 TD
[(kn)20.1(ow)18.2(n)-318.2(t)11(ha)17(t)-319.5(m)12.4(an)17(y)-315.3(p)0(a)18.4(t)11(ie)15.3(n)12.4(t)11(s)-322.4(a)0(n)22.5(d)-322.2(d)13.8(o)0(c)14.8(t)11(o)12.2(r)0(s)-309(w)0(e)18.2(r)0(e)-310.3(u)12.4(si)16.7(n)12.4(g)]TJ
T*
[(in)20.9(cr)16(e)12.2(a)0(s)18.2(i)0(n)15.5(g)-537.5(do)15.2(s)13.6(e)0(s)20.4(,)-542.8(an)17(d)-539(t)11(ha)17(t)-541.8(d)0(e)20.6(m)0(a)17.1(n)12.4(ds)-530.8(on)-533.6(ho)19.2(sp)16.5(i)13.9(t)0(a)15.7(l)]TJ
0 -1.1869 TD
[(ad)18.4(m)12.4(i)0(s)16.7(s)0(i)16.7(o)12.2(n)12.4(s)-533.8(an)22.5(d)-533.6(b)0(l)18.5(o)12.2(od)-521.4(do)20.6(na)17.1(t)11(i)0(o)20.7(n)0(s)-521.4(w)0(e)18.2(r)0(e)-521.7(i)0(n)20.9(c)0(r)16(e)12.2(as)18.2(in)20.9(g)]TJ
0 -1.1923 TD
[(dr)16.4(am)22.5(at)21.1(ic)16.5(al)18.5(ly)18.4(.)-401.9(T)10.2(he)-398.1(Mi)17.9(n)12.4(i)0(s)16.7(t)11(ry)-394(of)-397.2(H)14.6(e)0(a)16.9(l)0(t)19.6(h)-404.9(re)20.3(qu)17(e)12.2(s)0(t)19.2(e)12.2(d)-409(a)]TJ
T*
.0093 Tc
[(World)-486.4(H)-3.2(e)9.3(a)-6.4(lth)-487.7(O)-1(rganization)-487.7(\().9(WHO\))-486.9(consultancy)]TJ
0 -1.1869 TD
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[(and)-215.1(G)-.7(eorge)-216.6(Stamatoyannopoulos)-215.3(was)-215.3(s)-3.9(e)9.6(l)-7.6(ected.)-218.8(By)]TJ
0 -1.1923 TD
0 Tc
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T*
.0094 Tc
[(screening)-349.3(o)0(f)-345.9(c)1.2(ouple)9.4(s)-349.6(to)-346.9(ident)9.4(i)-9(fy)-343.8(carriers)-351(and)-345.4(p)-3.9(re-)]TJ
0 -1.1869 TD
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[(nat)8.9(a)-7.9(l)-215.6(d)-4.4(iagnosi)-4.3(s).8(,)-214.1()43.5(provid)-4.4(e)-.5(d)-215.8(t)-1.7(hey)-214.3(a)-2.7(re)-217.3(w)8.9(i)-9.1(ll)-4.3(ing)-214.3(t)-1.7(o)-217.3(h)-.4(ave)]TJ
0 -1.1923 TD
0 Tc
[(t)11(h)0(e)-322.2(a)0(f)23.3(f)0(e)20.1(c)0(t)19.1(e)0(d)-320.8(p)0(r)16.4(e)12.2(gn)16.9(an)22.5(cy)-318.1(te)17.9(rm)20.5(in)15.5(at)21.1(io)20.7(n.)17()56.3()]TJ
7.8454 0 0 6.9729 217.474 231.307 Tm
(17)Tj
10.4607 0 0 10.4607 229.4929 226.6582 Tm
-.0133 Tc
[(The)-342.5(r)-13.3(e)7(s)-13.3(ul)-13.3(t)6.3(s)]TJ
-17.9389 -1.1923 TD
0 Tc
[(o)12.2(f)-360.7(h)12.4(i)0(s)-351.9(c)13.4(on)19.2(su)15.2(l)13.9(t)0(a)15.7(n)12.4(cy)-350.6(w)11.4(e)12.2(re)-348.3(pr)16.4(e)12.2(s)0(e)20.4(n)0(t)18.1(e)0(d)-347.9(a)0(n)17(d)-354.8(ad)18.4(o)12.2(p)0(t)14(e)12.2(d)-354.8(b)0(y)]TJ
0 -1.1869 TD
[(t)11(h)0(e)-479.4(M)0(i)17.9(n)12.4(is)16.7(t)11(r)0(y)-480.7(i)0(m)20.9(m)0(e)19.3(d)0(i)16.9(a)0(t)21.1(e)12.2(ly)18.4(.)-488.6(A)-490.6(su)20.6(mm)19.5(ar)18.1(y)-488.7(w)11.4(as)-475(pu)15.4(b-)]TJ
0 -1.1923 TD
[(li)17(s)13.6(h)0(e)19.2(d)-311.4(in)-298.8(t)11(h)12.4(e)]TJ
/F8 1 Tf
6.0374 0 TD
[(Br)16.1(it)20.4(is)15.8(h)-307.3(M)0(e)22.8(d)0(i)14.8(c)0(a)21.8(l)-311.9(J)12.4(o)12.2(ur)15(n)12.4(a)0(l)]TJ
/F4 1 Tf
11.0723 0 TD
(.)Tj
7.8454 0 0 6.9729 223.6535 193.9464 Tm
(18)Tj
10.4607 0 0 10.4607 235.4456 189.2976 Tm
[(In)-297(h)12.4(i)0(s)-297.7(d)0(i)16.9(s)0(-)]TJ
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[(cu)20.4(ss)16.3(io)20.7(n)-188.1(h)0(e)-175.9(s)0(t)19.2(a)0(t)15.7(e)12.2(s:)-176.9()56.3()0(T)17.7(h)12.4(is)-178.4(sm)15.2(al)24(l)-192(M)0(e)21.7(d)0(i)16.9(t)11(e)12.2(r)0(r)16(a)0(n)17(e)12.2(an)-178.1(n)12.4(a)0(t)15.7(i)0(o)20.7(n)]TJ
0 -1.1869 TD
[(is)-319.3(thus)-324.4(burdened)-322.3(with)-319.7(one)-320.8(of)-321.4(the)-316.6(highest)-326.3(frequen-)]TJ
0 -1.1923 TD
[(cies)-234(of)-234.7(thalassaemia)-236(genes)-232.3(in)-233.8(man.)-236.9(The)-230.7(local)-234.5(public)]TJ
0 -1.1869 TD
[(health)-285.6(service)-290.6(has)-283.7(to)-280.2(face)-287.1(the)-284(problems)-283.1(of)-283.4(a)-282.6(severe)]TJ
0 -1.1923 TD
[(disease)-458(whose)-458.4(managemen)-9.6(t)-455(i)0(s)-454.8(completel)-9.4(y)-456.2(inade-)]TJ
T*
[(quate,)-351.5(whose)-355.4(cure)-349.5(is)-351.9(not)-349.1(in)-353(sight,)-351.8(and)-354(whose)-350(pre-)]TJ
0 -1.1869 TD
[(natal)-283.9(diagnosis)-287.6(is)-281.4(unavail)-9.5(able.)47.5()]TJ
1.1435 -1.1923 TD
[(The)-225.2(actions)-227.6(taken)-228.4(in)-228.4(Cyprus)-226.9(following)-228.2(his)-225.6(report)]TJ
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[(are)-251.5(well)-257.4(known,)-253.5(have)-253.5(resulted)-249.6(in)-255.5(the)-256.9(minimization)]TJ
0 -1.1869 TD
[(of)-185.9(new)-186.1(births,)-186.5(and)-191.4(as)-182.3(a)-190.5(result)-183.5(existing)-190.3(patients)-183.7(were)]TJ
0 -1.1923 TD
[(given)-180.1(the)-181.1(best)-180.7(possible)-178.5(resources)-181.4(to)-177.2(survive.)-181(If)-182.3(there)]TJ
T*
[(was)-398.5(no)-392.6(prevention,)-397.4(the)-397.9(increasing)-394.9(number)-398.5(of)-391.8(pa-)]TJ
25.4288 64.2875 TD
[(tients)-440.6(would)-434.8(have)-437.8(had)-440.7(little)-433.3(chance,)-441.7(even)-435.6(for)-438(an)]TJ
0 -1.1923 TD
[(adequate)-276.7(supply)-280.3(of)-283.4(blood.)]TJ
/F9 1 Tf
8.9663 0 0 8.9663 465.2219 666.6518 Tm
[(Dr.)-333.7(Michael)-338.6(Angastiniotis)]TJ
2.0613 -1.2267 TD
[(TIF)-341(Medical)-332.3(Advisor)]TJ
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[(Thalassaemia)-341.9(International)-343.8(Federation)]TJ
2.858 -1.2203 TD
[(PO)-328.8(Box)-337.3(28807,)-335.4(2083)-336.5(Strovolos)]TJ
8.8584 -1.2266 TD
(Cyprus)Tj
-11.4128 -1.8273 TD
(E-mail:)Tj
/F10 1 Tf
2.8327 0 TD
(thalassaemia@cytanet.com.cy)Tj
/F2 1 Tf
10.959 0 0 10.959 307.8424 564.3778 Tm
[(THE)-335.4(BRILLIANT)-326.1(GEORGE)]TJ
0 -1.1329 TD
[(STAMATOYANN)6.2(OPOULOS)]TJ
/F4 1 Tf
10.4607 0 0 10.4607 307.8424 538.0156 Tm
[(Writing)-350(about)-350.7(Dr.)-344.5(George)-351.3(Stamatoyannopou)7(los)-350.5(is)]TJ
0 -1.1923 TD
[(quite)-216.7(a)-217.6(challengewhat)-215.6(at)-217.4(rst)-220.5(glance)-220.7(may)-216.9(appear)]TJ
T*
[(as)-447.9(hyperbole)-453.4(is)-449.4(none)-449.3(other)-448.1(than)-447.2(an)-449(accurate)-451.3(re-)]TJ
0 -1.1869 TD
[(ection)-253.7(of)-256.3(an)-253.9(enormous)-251.2(personality)-253.7(and)-251(an)-253.9(equally)]TJ
0 -1.1923 TD
[(enormous)-278.3(body)-279.2(of)-278(work.)]TJ
1.1435 -1.1923 TD
[(George)-497.6(was)-496.1(already)-496.5(internationally)-494.5(known)-496.6(in)]TJ
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[(the)-473.7(early)-471.6(1960s)-471.9(when)-471.8(he)-473.9(moved)-470.5(from)-474.3(Greece)-472.4(to)]TJ
0 -1.1923 TD
[(Seattle,)-540.9(where)-539.8(he)-544.4(pursued)-542.4(a)-542.8(brilliant)-543.1(academic)]TJ
T*
[(career)-537.6(as)-540(professor)-538(of)-538.2(medicine,)-541.3(pathology,)-540.3(and)]TJ
0 -1.1869 TD
.0249 Tc
[(geno)4.6(me)-624.1(scien)4.8(c).4(es)-628.1(and)-627.9(d).7(ire)4.6(c).4(to)4.6(r)-628.3(o)-.8(f)-628.5(t)3.4(he)-629.5(Marke)4.6(y)]TJ
0 -1.1923 TD
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[(Molecular)-336.1(M)1.3(edicine)-337.3(C)5.3(enter)-336.1(a)1.9(t)-338.5(t)2.9(he)-337.3(University)-334.3(of)]TJ
T*
.0236 Tc
[(Washing)-4.5(t)2.1(on,)-405.4(p)-.6(roducing)-405.5(more)-408.6(than)-408.4(400)-405.4(original)]TJ
0 -1.1869 TD
.0101 Tc
[(p)2.2(u).8(bl)2.3(ica)3.9(t)-.5(ions)2(.)-202.1(H)-2.4(i)2.3(s)-203.9(res)2(e).7(arch)-205.1(led)-203.7(t)-.5(o)-199.9(t)-.5(he)-205.3(d)2.2(i)2.3(scove)10.1(r)-7.6(y)-202.2(a)-1.5(nd)]TJ
0 -1.1923 TD
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[(understanding)-506.6(of)-508.7(t)9.2(h)-5.3(e)-509.7(m)0(olecular)-508.5(mechanisms)-508.3(of)]TJ
T*
0 Tc
[(r)-8.2(e)-9.4(d)-414.4(b)0(l)24(o)0(o)19.1(d)-392.7(ce)20.2(ll)-384(pr)16.4(o)12.2(d)0(u)20.8(c)0(t)19.1(i)0(o)15.3(n)-388.6(du)15.4(r)13.4(i)0(n)15.5(g)-391.2(h)12.4(u)0(m)19.5(a)0(n)-384(o)12.2(nt)18.1(o)12.2(g)0(e)16.7(n)12.4(y)]TJ
0 -1.1869 TD
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/F5 1 Tf
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0 Tc
(c)Tj
/F4 1 Tf
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[(-globin)-278(a)-14(s)-266.8(a)]TJ
-17.9877 -1.1923 TD
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[(drug)-209(th)4.9(erap)-12.9(y)-195.2(f).3(or)]TJ
/F5 1 Tf
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(b)Tj
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[(-globinopathies,)-204(i)-13.5(n)-198.5(the)-207.2(a)-13.5(p)10.3(p).3(lica)-13.5(t)13(ion)]TJ
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[(of)-316(lentiviral)-314.2(gene)-310.9(therapy)-312.8(for)]TJ
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(b)Tj
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[(-thalassemia,)-309.5(or)-315.8(by)]TJ
-14.2861 -1.1923 TD
[(the)-305.7(inclusion)-304.4(of)-305.1(Cypriots)-305.1(in)-309.7(Georges)-303.1(effort)-303.9(to)-307.3(map)]TJ
T*
[(the)-246.1(distribution)-249.2(of)-245.5(Hellenic)-245.5(DNA)-247(around)-245.4(the)-246.1(globe.)]TJ
0 -1.1869 TD
[(George)-508.4(continues)-504.1(to)-507.8(look)-506.7(forward,)-503.9(and)-505.7(we)-507.5(keep)]TJ
0 -1.1923 TD
[(looking)-280.8(forward)-280.9(to)-274.8(his)-279.8(next)-279.6(visit)-284.5(to)-274.8(Cyprus!)]TJ
/F9 1 Tf
8.9663 0 0 8.9663 505.1337 569.0266 Tm
[(Carsten)-335.5(W.)-333.7(Lederer)]TJ
-.8157 -1.2266 TD
[(Marios)-336.9(S.)-337.9(Phylactides)]TJ
1.0369 -1.2203 TD
[(Marina)-331.8(Kleanthous)]TJ
-10.1293 -1.2203 TD
[(Molecular)-344.1(Genetics)-334.6(Thalassaemia)-341.9(Department)]TJ
-.6196 -1.2266 TD
[(The)-334.6(Cyprus)-337.1(Institute)-333.5(of)-334.3(Neurology)-339(and)-340.9(Genetics)]TJ
6.4557 -1.2203 TD
[(6)-330.7(International)-343.8(Airport)-338.3(Avenue)]TJ
6.4747 -1.2203 TD
[(1683)-336.5(Nicosia)]TJ
2.3964 -1.2267 TD
(Cyprus)Tj
-7.4674 -1.8336 TD
(E-mail:)Tj
/F10 1 Tf
2.8327 0 TD
(Lederer@cing.ac.cy)Tj
ET
1 i
q 1 0 0 1 62.022 447.023 cm 0 0 m
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Q
BT
/F1 1 Tf
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(REFERENCES)Tj
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.9745 -1.2519 TD
[(struction)-356.1(of)-353.2(a)-356.8(recombinant)-352.4(human)-355.7(parvovirus)-352.8(B19:)]TJ
0 -1.2448 TD
[(adeno-associat)5.4(ed)-706.5(virus)-702.5(2)-698.2(\(AAV\))-698.6(DNA)-700.5(inverted)]TJ
0 -1.2519 TD
[(terminal)-572.9(repeats)-565.5(are)-567.7(functional)-564.5(in)-572.7(an)-571.3(AAV-B19)]TJ
T*
[(hybrid)-549.1(virus.)-555.6(Proc)-545.5(Natl)-545.5(Acad)-551.9(Sci)-547.3(USA)-551.3(1989;86:)]TJ
T*
(80788082.)Tj
-.9745 -1.8708 TD
[(2.)-309.5(Kotin)-376.1(RM,)-364.6(Siniscalco)-368.9(M,)-373.8(Samulski)-368.8(RJ,)-371.4(et)-374.5(al.)-368.9(Site-)]TJ
.9745 -1.2519 TD
[(specic)-280.6(integrati)8.3(on)-279.7(by)-277.7(adeno-associ)10.1(ated)-277.2(virus.)-278.2(Proc)]TJ
T*
[(Natl)-332.1(Acad)-331.4(Sci)-333.9(USA)-330.8(1990;87:2)8.4(2112215.)]TJ
-.9745 -1.8708 TD
[(3.)-309.5(Ozawa,)-367.2(K,)-363.2(Kurtzman,)-356.3(G,)-368.1(and)-366.2(Young,)-360.6(N.)-363(Productive)]TJ
.9745 -1.2519 TD
[(infection)-542.1(by)-540.8(B19)-540.8(parvovirus)-537.8(of)-545.3(human)-533.5(erythroid)]TJ
T*
[(bone)-253.5(marrow)-242.2(cells)-246.2(in)-245.5(vitro.)-247(Blood)-245.7(1987;70:3843)7.1(91.)]TJ
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[(4.)-309.5(Ozawa)-243.8(K,)-242.3(Ayub)-238.9(J,)-238.4(Hao)-239.8(YS,)-240.2(et)-246.5(al.)-240.9(Novel)-243.5(transcript)10.2(ion)]TJ
.9745 -1.2519 TD
[(map)-339.2(for)-335.4(the)-333(B19)-341.6(\(human\))-332.3(pathogenic)-333.1(parvovirus.)-334(J)]TJ
T*
[(Virol)-334.8(1987;61:239)6.2(52406.)]TJ
-.9745 -1.8708 TD
[(5.)-309.5(Srivastava)-349.6(A,)-346.8(and)-344.8(Lu,)-344.2(L.)-350.2(Replication)-348.1(of)-346.1(B19)-341.6(parvo-)]TJ
.9745 -1.2519 TD
[(virus)-439.3(in)-444.7(highly)-441.4(enriched)-437.6(hematopo)8.4(ietic)-442.7(progenitor)]TJ
T*
[(cells)-516.5(from)-508.7(normal)-510(human)-512.2(bone)-516.7(marrow.)-507.9(J)-513.3(Virol)]TJ
0 -1.2448 TD
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(1988;62:30593063.)Tj
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0 Tc
[(6.)-309.5(Walsh)-401.5(CE,)-399.9(Liu)-401.1(JM,)-403.4(Xiao)-393.9(X,)-405.9(et)-395.9(al.)-404.5(Regulated)-402(high)]TJ
.9745 -1.2519 TD
[(level)-433.2(expression)-428.7(of)-431.4(a)-427.9(human)-433.9(gamma-glob)10.4(in)-430.4(gene)]TJ
T*
-.0273 Tc
[(i)-8.5(n)0(trodu)-7.1(ced)-291.6(i)-1.4(nto)-284.5(e)-7.1(ry)-5.1(throi)-8.5(d)-284.5(ce)-7.1(lls)-282.5(b)-7.1(y)-282.5(an)-291.6(ade)-7.1(no-as)-5.1(so)-7.1(cia)-7.1(t)-2.4(ed)]TJ
0 -1.2448 TD
0 Tc
[(virus)-553.1(vector.)-550.6(Proc)-545.5(Natl)-545.5(Acad)-551.9(Sci)-547.3(USA)-551.3(1992;89:)]TJ
0 -1.2519 TD
(72577261.)Tj
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[(7.)-309.5(Zhou)-381.5(SZ,)-378.6(Li)-385.7(Q,)-375.2(Stamatoyanno)6.7(poulos)-383.1(G,)-382.3(Srivastava)]TJ
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[(A.)-289.9(Adeno-associ)8.4(ated)-291.4(virus)-289.9(2-mediate)10.6(d)-292.8(transduction)]TJ
22.0009 34.9966 TD
[(and)-408.8(erythroid)-400.8(cell-specic)-403.2(express)10(ion)-410.2(of)-403(a)-406.6(human)]TJ
/F5 1 Tf
0 -1.2519 TD
(b)Tj
/F10 1 Tf
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[(-globin)-326(gene.)-334.2(Gene)-333.4(Ther)-327(1996;3:223229.)]TJ
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[(8)14.8(.)-294.7(Ponnazha)6.6(gan)-320.6(S,)-322(Yoder)-315.9(MC,)-322(S)2.7(rivastava)-320.6(A)4.9(.)-322(A)4.9(deno-)]TJ
.9745 -1.2519 TD
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[(associ)5.9(ated)-319.9(virus)-325(t)4.9(ype)-327.1(2).1(-medi)5.9(ated)-319.9(transductio)7.3(n)-327.1(of)]TJ
T*
.015 Tc
[(murine)-548.1(he)6.8(matopoietic)-546.1(cells)-546.1(w)5.3(i)-1.7(th)-541(long-term)-549.6(re-)]TJ
T*
.0153 Tc
[(populating)-362.8(abili)5.7(ty)-367.9(and)-362.8(sustai)5.7(ned)-369.9(expression)-369.9(o)7.1(f)-372.3(a)]TJ
0 -1.2448 TD
[(human)-263.1(globin)-263.1(gene)-270.3(in)-263.1(v)-5.1(i)5.8(vo.)-271.6(J)-270.3(Virol)-271.6(1997)7.2(;71:309)7.2(8)]TJ
0 -1.2519 TD
(3104.)Tj
-.9745 -2.1268 TD
0 Tc
[(9.)-309.5(Tan)-245.2(MQ,)-241.5(Qing)-235.2(KY,)-247.3(Zhou)-239.3(SZ,)-243.4(et)-239.4(al.)-240.9(Adeno-associa)7.2(ted)]TJ
.9745 -1.2448 TD
[(virus)-446.4(2-mediated)-445.8(transduction)-444.9(and)-451.5(erythroid)-443.5(line-)]TJ
0 -1.2519 TD
[(age-restricted,)-340.6(long-term)-347.5(expression)-343.3(of)-346.1(the)-347.2(human)]TJ
/F5 1 Tf
T*
(b)Tj
/F10 1 Tf
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[(-globin)-411.4(gene)-410(in)-416.2(hematopoiet)8.3(ic)-414.2(cells)-416.9(from)-409.2(homo-)]TJ
-.5548 -1.2519 TD
(zygous)Tj
/F5 1 Tf
2.7812 0 TD
(b)Tj
/F10 1 Tf
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[(-thalassemic)-329.5(mice.)-335.1(Mol)-332.3(Ther)-334.1(2001;3:940)7.3()]TJ
-3.3289 -1.2448 TD
(946.)Tj
-.9745 -2.0059 TD
[(10.)-310.6(Maina)-434.1(N,)-427(Zhong)-432.4(L,)-435.5(Li,)-430.9(X,)-434.3(et)-431.4(al.)-432.9(Optimization)-424.2(of)]TJ
1.4226 -1.2448 TD
[(recombinan)6.8(t)-565.5(adeno-associat)5.4(ed)-564.2(viral)-563.6(vectors)-561.5(for)]TJ
0 -1.2519 TD
[(human)-426.8(beta-globin)-432.5(gene)-424.2(transfer)-429.2(and)-430.2(transgene)]TJ
T*
[(expression.)-331.6(Hum)-326.7(Gene)-333.4(Ther)-334.1(2008;19:3)8.4(65375.)]TJ
-1.4226 -1.8708 TD
[(11.)-310.6(Ma)25.9(in)17.7(a,)-373.5(N)16.5(,)-386.6(Ha)24.5(n,)-373.5(Z,)-373.5(L)15.1(i)0(,)-374.9(X)0(,)-370.3(e)0(t)-374.5(a)0(l)17.7(.)-379.5(Re)22.3(co)21.1(mb)24.7(in)24.8(an)19.1(t)-380.5(s)0(e)21.1(l)0(f)22.4(-)]TJ
1.4226 -1.2519 TD
[(co)21.1(mp)24.7(le)24.8(me)17.6(nt)23.8(ar)23.8(y)-653.5(a)0(d)26.2(e)0(n)19.1(o)0(-)23.8(a)0(s)28.2(s)0(o)21.1(c)0(i)19.7(a)0(t)23.8(e)0(d)-642.4(v)15.1(ir)22.4(us)-640.4(se)21.1(ro)23.8(ty)25.8(pe)]TJ
T*
[(ve)21.1(c)15.1(t)0(o)23.8(r)0(-)21.4(m)0(e)24.7(d)0(i)17.7(a)0(t)23.8(e)0(d)-614(h)0(e)26.2(m)0(a)24.7(t)0(o)23.8(p)0(o)19.1(i)0(e)24.8(t)0(i)22.4(c)-625.1(st)25.8(em)-615.5(c)15.1(e)0(l)17.7(l)-621.4(tr)21.4(an)19.1(s)15.1(-)]TJ
T*
[(du)19.1(c)15.1(t)0(i)22.4(o)0(n)-244.1(a)0(n)19.1(d)-257.2(li)23.4(ne)26.2(ag)19.1(e-)23.8(re)23.8(s)15.1(t)0(r)21.4(i)0(c)19.7(t)0(e)23.8(d)0(,)-245.5(l)0(o)24.8(n)0(g)19.1(-)0(t)21.4(e)0(r)23.8(m)-251.6(tr)21.4(an)26.2(sg)21.1(en)19.1(e)]TJ
0 -1.2448 TD
[(ex)21.1(pr)23.8(es)21.1(s)15.1(i)0(o)17.7(n)-363.9(in)-352.2(a)-371(m)0(u)24.7(r)0(i)22.4(n)0(e)-357.9(s)15.1(er)23.8(ia)17.7(l)-365.3(b)0(o)26.2(n)0(e)-357.9(m)0(a)24.7(r)0(r)21.4(o)0(w)-352.3(t)24.9(r)24.9(a)20.2(n)27.3(s)22.2(-)]TJ
0 -1.2519 TD
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[(p)-6.7(l)-1(an)-6.7(tati)-8.1(on)-305.4(m)-8.2(ode)-6.7(l.)-306.8(Hu)-6.7(m)-306.9(G)-1.3(en)-6.7(e)-305.4(T).4(h)-6.7(e).4(r)-307.8(2).4(0)-6.7(0).4(8)-6.7(;)-1(1)-6.7(9).4(:3)-6.7(76)-6.7(3)-6.7(83)-6.7(.)]TJ
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0 Tc
[(12.)-310.6(Song)-314.3(L,)-314.6(Kauss)-318.5(MA,)-312.6(Kopin)-309.7(E,)-316.6(et)-317.6(al.)-319.1(Optimizing)-305.8(the)]TJ
1.4226 -1.2448 TD
[(transduction)-466.2(efciency)-470.2(of)-467(capsid-modied)-466.6(AAV6)]TJ
22.0009 34.9966 TD
[(serotype)-315.7(vectors)-312.5(in)-316.6(primary)-319.4(human)-313(hematopoieti)5.8(c)]TJ
0 -1.2519 TD
[(stem)-226.9(cells)-232(in)-238.4(vitro)-230.3(and)-231(in)-231.3(a)-235.9(xenograft)-228.7(mouse)-232.8(model)]TJ
0 -1.2448 TD
[(in)-330.8(vivo.)-331.6(Cytotherapy)-332.5(2013;15:9)8.4(86998.)]TJ
-1.4226 -1.8779 TD
[(13.)-310.6(Song)-449.4(L,)-449.7(Li)-449.7(X,)-448.6(Jayandharan)-446.7(GR,)-451.4(et)-445.7(al.)-454.3(High-ef-)]TJ
1.4226 -1.2519 TD
[(ciency)-528.5(transduction)-523.1(of)-523.9(primary)-525.7(human)-526.4(hemato-)]TJ
0 -1.2448 TD
[(poietic)-295.6(stem)-298(cells)-296(and)-295(erythroid)-294.1(lineage-rest)7(ricted)]TJ
0 -1.2519 TD
[(expression)-272.2(by)-277.7(optimized)-280.2(AAV6)-275(serotype)-273(vectors)-276.9(in)]TJ
T*
[(vitro)-465(and)-472.9(in)-473.1(a)-463.5(murine)-467.3(xenograft)-470.6(model)-470.9(in)-466(vivo.)]TJ
T*
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[(PLoS)-333.8(One)-325.4(2013;8:e58757.)]TJ
-1.4226 -1.8708 TD
0 Tc
[(14.)-310.6(Sather)-371.1(BD,)-373.1(Romano)-367.9(Ibarra)-375.7(GS,)-366(Sommer)-371.8(K,)-370.3(et)-374.5(al.)]TJ
1.4226 -1.2519 TD
[(Efcient)-397.3(modication)-401.2(of)-403(CCR5)-400.3(in)-402(primary)-404.8(human)]TJ
T*
[(hematopoiet)8.3(ic)-506.7(cells)-495.2(using)-502.9(a)-499.1(megaTAL)-499.9(nucleas)9(e)]TJ
0 -1.2448 TD
[(and)-408.8(AAV)-401.9(donor)-413.5(template.)-403.3(Sci)-412.1(Transl)-406.9(Med)-402(2015;)]TJ
0 -1.2519 TD
[(7:307ra156)6.3(.)]TJ
-1.4226 -1.8779 TD
[(15.)-310.6(Wang)-244.5(J,)-238.4(Exline)-242.3(CM,)-243.7(DeClercq)-236.9(JJ,)-246.6(et)-246.5(al.)-240.9(Homology-)]TJ
1.4226 -1.2448 TD
[(driven)-285.9(genome)-292.8(editing)-290.5(in)-288.2(hematopoieti)5.8(c)-290.8(stem)-290.9(and)]TJ
0 -1.2519 TD
[(progenitor)-375.5(cells)-381.4(using)-374.9(ZFN)-382.1(mRNA)-371(and)-380.4(AAV6)-374.6(do-)]TJ
T*
-.0001 Tc
[(nors.)-334.7(Nat)-329.7(Biotechnol)-324.3(2015;33:12561263.)]TJ
-1.4226 -1.8708 TD
0 Tc
[(16.)-310.6(De)-288.5(Ravin)-286.3(SS,)-290(Reik)-285.2(A,)-289.9(Liu)-287.3(PQ,)-291(et)-289.2(al.)-290.7(Targeted)-284.1(gene)]TJ
1.4226 -1.2519 TD
[(addition)-320.1(in)-323.7(human)-320.1(CD34)]TJ
/F7 1 Tf
8.9768 0 TD
(+)Tj
/F10 1 Tf
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[(hematop)9.5(oietic)-322.9(cells)-324.5(for)]TJ
-9.8517 -1.2519 TD
[(correction)-335.9(of)-339(X-linked)-343.3(chronic)-334.9(granulomatou)7.2(s)-340.5(dis-)]TJ
T*
[(ease.)-332.2(Nat)-329.6(Biotechnol)-331.3(2016;34:42)7.3(4429.)]TJ
-1.4226 -1.8708 TD
[(17.)-310.6(World)-427.2(Health)-431.9(Organizat)10.2(ion.)-434.1(Tech)-429.3(Rep)-427(Ser)-429.4(1972;)]TJ
1.4226 -1.2519 TD
(509:20,40.)Tj
-1.4226 -1.8779 TD
[(18.)-310.6(Ashiotis)-339.1(TH,)-340.8(Zachariadis)-340.7(Z,)-345.1(Sofronia)9.3(dou,)-347.3(K,)-341.9(et)-339(al.)]TJ
1.4226 -1.2448 TD
[(Thalassaemia)-319.7(in)-316.6(Cyprus.)-324.5(Br)-321.5(Med)-316.7(J)-321.2(1973;2:3841.)]TJ
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