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[(th)21.4(e)-309.7(t)12.2(wo)-288.9(IC)23(P4)-298(l)15.4(o)0(c)23.2(i)-307(sh)26.9(ow)20.9(e)12.8(d)-306.5(t)12.2(h)0(a)22.4(t)-304(t)12.2(r)0(e)18.4(a)13.1(t)12.2(m)0(e)21.5(n)15.6(t)-310.3(o)16.2(f)-310.3(p)0(a)24.4(t)12.2(ie)21.9(n)15.6(t)0(s)-299(w)0(a)24.2(s)-304.8(we)23.8(l)15.4(l)]TJ
0 -1.2203 TD
[(to)22(le)21.9(ra)25.1(t)12.2(e)0(d)-312.7(w)0(i)20.1(t)12.2(h)-325.9(n)15.6(o)-325.2(s)0(e)24.1(r)0(i)21.1(o)0(u)21.2(s)-323.8(a)13.1(d)16(ve)18.3(rs)23.3(e)-322.4(e)12.8(ve)24.7(nt)21.4(s,)-314.1(a)13.1(n)0(d)-309.9(t)12.2(ha)22.4(t)-322.9(s)0(u)22.6(b)0(j)22.2(e)12.7(ct)19.2(s)-323.8(i)15.4(n)]TJ
T*
[(th)21.4(e)-385.6(m)0(i)24.2(d)0(d)25.6(l)0(e)21.9(-)-386.2(a)13.1(n)0(d)-373.1(h)0(i)24.7(g)0(h)17.5(-)12.2(d)16(o)0(s)21.2(e)-385.6(c)13.4(o)0(h)19.1(o)16.2(rt)17.8(s)-380.7(r)0(e)18.4(p)0(o)27.5(r)0(t)17.8(e)12.8(d)-382.4(s)0(u)22.6(b)14.6(st)17.2(a)13.1(n)15.6(ti)21.3(a)13.1(l)-389.2(pa)24.4(i)15.4(n)]TJ
0 -1.2266 TD
[(re)18.4(l)15.4(i)0(e)21.9(f)12.2(,)-458.2(w)0(i)20.1(t)12.2(h)-458.6(t)12.2(ho)25.5(se)-450.1(i)15.4(n)-458.6(th)21.4(e)-461.5(h)15.6(ig)23.7(h-)21.4(do)19.5(se)-443.8(gr)20.2(o)16.2(u)0(p)-451.6(h)15.6(av)18.7(i)15.4(n)0(g)-450.4(t)12.2(h)15.6(e)0(i)21.9(r)-462.3(pa)24.4(i)15.4(n)]TJ
0 -1.2203 TD
-.0138 Tc
[(s)-13.8(c)4.6(or)-13.8(e)4.6(s)-375.5(dr)-13.8(o)8(p)-375.6(fr)-13.8(o)8(m)-378.1(810)-380(do)-13.8(w)7.1(n)-377.6(to)-377(12)-373.7(\(F)-13.8(i)9.9(n)-13.8(k)]TJ
/F8 1 Tf
18.7221 0 TD
0 Tc
[(et)-348.9(a)13.4(l)]TJ
/F4 1 Tf
1.7388 0 TD
[(.,)-347.3(20)19.9(1)13.1(1)13.1(\))12.2(.)-363.3(H)12.7(ow)20.9(-)]TJ
-20.4609 -1.2203 TD
[(ev)18.3(e)12.8(r)0(,)-484.2(i)0(t)-484.5(i)0(s)-485.4(n)0(o)19.1(t)-493.7(k)14.6(n)0(o)19.1(w)0(n)-485.6(w)0(h)26.6(e)0(t)18.6(h)0(e)22(r)-493.9(t)12.2(h)0(i)18.4(s)-494.5(ne)22(wl)26.5(y)-497.6(e)12.8(ng)17.5(i)15.4(n)0(e)22(e)12.7(re)18.4(d)-496.2(N)12.7(P2)]TJ
0 -1.2266 TD
[(ve)18.3(c)13.4(t)12.2(or)-490.3(t)12.2(h)0(a)22.4(t)-500(e)12.7(n)0(c)22.6(o)0(d)25.8(e)0(s)-488.1(h)0(P)20.5(P)0(E)20.9(,)-496.1(or)-490.3(a)-499(s)0(i)26.8(m)0(i)24.2(l)0(a)22.3(r)-500.2(ve)24.7(c)13.4(t)0(o)22.1(r)-500.2(vH)24.6(PP)22.6(E)-502.5(t)12.2(ha)22.4(t)]TJ
0 -1.2203 TD
[(co)23.2(nt)21.4(a)13.1(i)0(n)18.4(s)-311.1(a)13.1(n)-313.2(H)12.7(C)12.5(M)13.9(V)-312.6(IE)-296(pr)23.2(om)18.6(o)16.2(t)0(e)18.6(r)0(-)24.1(h)0(P)20.5(P)0(E)-295.2(e)0(x)23.2(p)0(r)23.2(e)0(s)17.8(s)0(i)26.8(o)0(n)-303.3(i)15.4(n)-313.2(t)12.2(he)-300.5(IC)23(P4)]TJ
T*
[(lo)19(c)13.4(i)-256.4(of)-243.5(a)-258.8(r)0(e)24.7(p)0(l)20.4(i)15.4(c)13.4(a)0(t)19(i)15.4(on)19.1(-)12.2(d)0(e)22.4(f)12.2(e)12.8(c)0(t)19.2(i)15.4(ve)-247.2(H)12.7(S)0(V)-247.9(v)0(e)24.7(c)13.4(t)12.2(o)0(r)-250.1(d)16(el)21.9(e)12.8(t)0(e)18.6(d)-255.9(f)12.2(o)0(r)-243.7(I)0(C)23(P)0(4)-247.5(a)13.1(n)15.6(d)]TJ
T*
[(IC)23(P2)24.4(7,)-362.8(c)13.4(a)13.1(n)-370.1(b)0(e)-358.4(a)13.1(pp)22.6(li)24.6(ed)-363.3(t)12.2(o)-369.5(t)12.2(h)0(e)-357.4(t)0(r)17.8(e)12.7(a)13.1(t)12.2(me)21.5(nt)-357.9(of)-357.3(bl)23.7(ad)22.8(de)22.4(r)-373.8(h)15.6(yp)19.5(e)12.8(r)0(s)23.3(e)12.8(n-)]TJ
0 -1.2266 TD
[(si)20.4(t)12.2(i)0(v)21(e)-227.5(d)16(i)0(s)20.4(o)0(r)21.8(d)16(er)18.4(s)-228.9(s)17.7(uc)18.3(h)-224.7(a)13.1(s)-228.9(B)0(P)20.9(S)14.2(/I)20.2(C)12.5(.)-224.2(Th)18.9(us)22.6(,)-224.2(i)0(n)-215.6(t)12.2(he)-218.3(c)13.4(u)0(r)23.2(r)0(e)18.4(n)15.6(t)-228.1(s)0(t)23.5(u)0(d)20.9(y)0(,)-216(t)12.2(he)]TJ
0 -1.2203 TD
[(vH)18.2(PP)22.6(E)-382.4(\()12.2(E1)22.8(G)13.9(6)13.1(-)12.2(E)0(N)22.3(K)0(\))-376.3(v)0(e)24.7(c)13.4(t)12.2(o)0(r)-376.5(t)12.2(ha)22.4(t)-386.2(i)15.4(s)-387(s)0(i)26.8(m)0(i)24.2(l)0(a)22.2(r)-386.4(t)12.2(o)-382.1(t)12.2(h)0(e)-376.3(N)12.7(P2)-367.6(ve)18.3(c)13.4(t)12.2(or)]TJ
T*
[(wa)24.2(s)-412.3(i)0(n)24.7(j)0(e)20.4(c)13.4(t)12.2(e)0(d)-401.2(i)0(n)24.7(t)12.2(o)-413.8(t)12.2(he)-401.6(b)14.6(l)0(a)22.2(d)16(de)22.4(r)-411.7(w)0(a)24.2(l)0(l)-399.1(t)12.2(o)-413.8(e)12.8(xa)23.6(m)15.1(i)0(n)24.7(e)-410.9(th)21.4(e)-410.9(e)12.7(ff)18(e)12.7(c)13.4(t)12.2(s)-412.3(of)]TJ
0 -1.2266 TD
[(vH)18.2(PP)22.6(E)16(-)12.2(me)21.5(di)25.1(at)19(e)12.8(d)-363.4(hP)20.6(PE)-352.1(de)22.4(l)15.4(i)0(v)21(e)12.8(ry)-352.9(on)-353.9(bl)23.7(a)13.1(d)0(d)19.3(e)12.8(r)-361.1(o)0(v)21.8(e)12.7(ra)18.8(c)13.4(t)12.2(iv)21(i)15.4(t)0(y)-352.6(a)0(n)22.4(d)]TJ
0 -1.2203 TD
[(pa)18.1(i)15.4(n)-319.5(be)21(ha)22.4(vi)21(o)16.2(r)-323.2(in)24.7(du)20.9(c)13.4(e)12.8(d)-325.5(b)14.6(y)-320.6(n)0(o)19.1(c)13.4(ic)22.5(e)12.8(p)0(t)23.5(i)0(v)21(e)-322.4(st)23.5(im)24.2(ul)20.4(i)-319.7(i)15.4(n)-325.9(r)0(a)25.1(t)12.2(s.)]TJ
/F3 1 Tf
28.0042 47.6684 TD
[(Materials)-332.7(and)-331.9(Methods)]TJ
/F10 1 Tf
0 -1.8336 TD
[(Viral)-333.5(vectors)]TJ
/F4 1 Tf
1.1128 -1.8336 TD
.014 Tc
[(The)-580.2(v).6(HG)-579.1(cont)-5.4(rol)-577.6(v).6(ec)-4.3(tor)-581.1(\().9(Fig.)-576.9(1\))-574.5(u)-6.3(s)0(ed)-577(in)-577.4(the)-573.9(s)0(t)-5.4(u)0(dies)]TJ
-1.1128 -1.2203 TD
.0145 Tc
[(\(Sriniva)-4(san)]TJ
/F8 1 Tf
5.3176 0 TD
.0126 Tc
[(et)-240.8(al)]TJ
/F4 1 Tf
1.7135 0 TD
.0132 Tc
[(.,)-242.6(20)-5.3(07\))-240.2(is)-241(a)-239.2(r)-.1(ep)-7.1(lic)-5(a)1(t)-6.2(i)-3(on-)-6.2(d)-2.4(ef)-6.2(ec)-5(tive)-239.6(H)-5.7(S)2.1(V-)-6.2(base)-5.7(d)]TJ
-7.0311 -1.2266 TD
.0158 Tc
[(vector)-421.2(deleted)-423.5(f)-3.6(or)-421.2(the)-426.7(e)3.3(ssen)]TJ
12.9556 0 TD
[(ti)5.9(al)-424(IE)-429.8(g)5.1(e)-3.1(nes)-428.1(I)1(CP4)-426.3(a)-2.7(nd)-423.5(ICP27)]TJ
-12.9556 -1.2203 TD
.0153 Tc
[(with)-399.1(an)-399.1(HCMV)-404.8(IE)-398.7(promoter-d)]TJ
14.176 0 TD
.0158 Tc
[(riven)-398.6(e)3.3(nhanced)-398.2(green)-398.6().2(uo-)]TJ
-14.176 -1.2203 TD
.0152 Tc
[(rescent)-516.4(p)1.2(rot)-4.2(e)2.7(in)-513(\()-4.2(e)2.7(GFP)-5.1(\))-510.1(gene)-515.8(expression)-513(cas)-5.1(s)1.2(et)-4.2(te)-515.8(inserted)]TJ
0 -1.2266 TD
[(into)-354.2(both)-348.5(ICP4)-350.9(loci)-355(\(Fi)5.4(g)-1.8(.)-354.4(1)3.1(\).)-354.3(In)-348.5(addi)5.4(tion,)-348(t)-4.1(he)-351.3(promoters)-352.7(f)2.2(or)]TJ
0 -1.2203 TD
.015 Tc
[(two)-329.2(o)-.4(ther)-327.1(IE)-323.1(genes,)-329.4(ICP22)-326(a)2.8(nd)-329.4(ICP)-5.3(47,)-329.4(were)-326.3(altered)-329.4(s)1(o)-322.9(t)-4.4(hat)]TJ
T*
.0173 Tc
[(t)4.2(h)1.3(e)-286.1(s)3.3(eq)6.6(uenc)5.4(es)-281.2(tha)5.1(t)-286.7(e)4.8(n)1.3(ab)6.6(le)-286.1(t)4.2(h)1.3(em)-277.4(to)-282.6(be)-279.8(expr)4(essed)-282.9(a)5.1(s)-287.5(I)2.5(E)-282.9(g)6.6(ene)4.8(s)]TJ
T*
.014 Tc
[(ar)-5.7(e)-302(a)-4.5(lt)-5.4(er)-5.7(ed;)-305.1(t)-5.4(hus,)-305.1(t)-5.4(h)-2(ese)-308.4(t).9(w)-6.6(o)-304.9(IE)-305.1(gene)-308.4(products)-309.8(ar)-5.7(e)-302(n)-2(o)-304.9(l)-2.2(onger)]TJ
0 -1.2266 TD
.0137 Tc
[(exp)-6.6(r).4(es)-6.6(sed)-457.2(d)-1.9(uring)-458.6(i)-2.5(nf)-5.7(ec)-4.5(tion)-457.6(exc)-4.5(e)-5.2(pt)-454.7(whe)-5.2(n)-451.3(IC)-5.4(P4)-453.7(and)-457.2(I)-1.1(C)-5.4(P)-.3(27)]TJ
0 -1.2203 TD
.0161 Tc
[(are)-420.1(s)-4.2(upplied)-423.2(i)-.1(n)-423.6(t)-3.3(rans)-427.8(via)-426(t)3(heir)-420.9(expressi)6.2(on)-429.9(in)-423.6(th)6.4(e)-426.4(7)-2.4(b)-424.6(c)4.2(om-)]TJ
T*
.0153 Tc
[(plementing)-349.5(cell)-355(l)5.4(i)-.9(ne)-351.3(used)-354.4(to)-354.2(propagate)-351.3(t)2.2(he)-357.6(virus)-352.7(\()-86.3(Marconi)]TJ
/F8 1 Tf
0 -1.2266 TD
.0158 Tc
[(et)-345.1(al)]TJ
/F4 1 Tf
1.821 0 TD
.0141 Tc
[(.,)-349.2(19)-4.4(96)-4.4(;)-349.2(K)-1.4(risky)]TJ
/F8 1 Tf
6.892 0 TD
.0197 Tc
[(et)-341.2(a)7.8(l)]TJ
/F4 1 Tf
1.8273 0 TD
.0168 Tc
[(.,)-340.2(19)4.6(98)4.6(b\))3.7(,)-346.5(w)2.5(her)3.5(e)-343.5(the)4.3(y)-348(a)4.6(r)-2.9(e)-343.5(e)-2.1(xpr)3.5(e)-2.1(ssed)]TJ
-10.5403 -1.2203 TD
.0162 Tc
[(as)-535.2(earl)6.3(y)-538.3(g)5.5(enes.)-530.5(T).6(his)-535.2(a)-2.3(l)6.3(t)-3.2(ernati)6.3(on)-537.3(means)-535.2(t)3.1(hat)-534.4(i)0(nfecti)6.3(on)-537.3(of)]TJ
T*
.0141 Tc
[(ev)-5.6(ery)-432.9(c)-4.2(ell)-438.4(t)1(hat)-435.3(d)-1.5(oe)-4.8(s)-429.8(n)-1.9(ot)-435.3(e)-4.8(x)-.7(pre)-4.8(s).1(s)-436.1(I)-.7(CP4)-434.3(a)-4.4(nd)-431.5(ICP)-6.2(2)1.9(7)-434.3(r).8(e)-4.8(n)-1.9(ders)]TJ
0 -1.2266 TD
.0153 Tc
[(vHG)-287(d)-.3(efectiv)-4.4(e)-288.1(in)-291.6(ex)-5.8(pression)-291.6(of)-288.7(f)-4.1(o)-.1(ur)-288.9(HSV)-291(I).5(E)-291.2(g)4.6(enes,)-291.1(m)-1.2(aking)]TJ
0 -1.2203 TD
.0157 Tc
[(it)-452.7(sig)5(n)-.3(icantly)-450.3(less)-453.5(toxic)-451.5(t)-3.7(han)-455.6(t)2.6(he)-452.1(previously)-450.3(tested)-448.9(HSV)]TJ
T*
.0141 Tc
[(ve)-4.8(ct)-5.3(or)-378.6(S)-3.3(H)1.5(P)-6.2(E)-1.5(,)-380.8(w)-.2(hich)-387.6(is)-379.2(de)-4.8(fe)-4.8(ct)-5.3(iv)-5.6(e)-384.1(i)4.2(n)-387.6(e)1.6(xp)-6.2(res)-6.2(s).1(ion)-381.3(o)-1.3(f)-384.7(o)-1.3(nly)-382.3(t)1(he)]TJ
T*
.0151 Tc
[(ICP4)-332.2(IE)-329.3(gene)-326.2(\(Krisky)]TJ
/F8 1 Tf
9.927 0 TD
.019 Tc
[(et)-322.9(al)]TJ
/F4 1 Tf
1.8084 0 TD
.0137 Tc
[(.,)-330.7(19)-4.8(98b\).)-330.6(The)-334(v).3(ec)-4.6(tor)-334.8(v).3(HP)-6.6(PE)-330.7(was)]TJ
-11.7353 -1.2266 TD
.0148 Tc
[(enginee)-4.1(r)1.5(ed)-569.9(f)-4.6(r)1.5(om)-570.8(vH)-4.1(G)-572(b)4.1(y)-571.3(r)1.5(e)-4.1(p).8(lac)-3.4(e)2.3(me)-4.1(nt)-567.4(of)-573.7(the)-573.1(e)2.3(G)-2.9(F)4.1(P)-574.6(e)2.3(x-)]TJ
0 -1.2203 TD
.0151 Tc
[(pression)-298.1(cassett)-4.3(e)-294.6(w).8(ith)-298.1(a)2.9(n)-298.1(H)2.5(C)-4(M)3.7(V)-297.5(I).3(E)-297.7(p)1.1(romot)-4.3(e)2.6(r-)-4.3(driven)-291.8(hPP)-5.2(E)]TJ
T*
.0143 Tc
[(ca)-4.2(sse)-4.6(tt)-5.1(e)-333.4(i)-1.9(n)-336.8(a)-333(manne)-4.6(r)-334.2(s).3(imila)-4.2(r)-334.2(to)-336.2(t)-5.1(h)-1.7(at)-333.9(f)-5.1(o)-1.1(r)-334.2(t)1.2(he)-339.7(cons)-6(tru)-6(c)2.4(tion)-336.8(of)]TJ
0 -1.2266 TD
.0151 Tc
[(the)-478(v)1.7(HGlyR)-469.7(v)-4.6(ector)-478.8(\()2(Srinivasan)]TJ
/F8 1 Tf
14.9284 0 TD
.0126 Tc
[(et)-481.1(al)]TJ
/F4 1 Tf
1.9538 0 TD
.0179 Tc
[(.)8.7(,)-471.9(20)5.7(07)5.8(\).)-465.6(This)-470.3(vH)5.3(PPE)]TJ
-16.8822 -1.2203 TD
.0158 Tc
[(isolate)-357.1(d)6.5(isplays)-352.2(s)-4.5(om)5.6(e)-357.2(s)-4.5(i)5.9(m)-.7(ila)]TJ
12.8355 0 TD
.0138 Tc
[(r)-5.9(i)-2.4(ty)-357.3(to)-362(the)-359.2(N)-5.1(P2)-358.8(ve)-5.1(ct)-5.6(or)-353.6(u)-6.5(s)-.2(ed)-362.2(in)]TJ
-12.8355 -1.2203 TD
.0158 Tc
[(the)-281.3(p)1.8(hase-I)-277.2(human)-284.8(c)3.9(linical)-278.6(trial)-278.6(\()2.7(Fink)]TJ
/F8 1 Tf
16.9833 0 TD
.0126 Tc
[(et)-285(al)]TJ
/F4 1 Tf
1.7514 0 TD
.0176 Tc
[(.,)-276.2(20)5.4(11)5.4(\).)-276.2(v)4.2(H)-1.3(G)-272(a)-.9(nd)]TJ
-18.7348 -1.2266 TD
.0174 Tc
[(v)4(H)-1.5(PPE)-295.4(we)4.9(r)4.1(e)-298.6(pr)4.1(opag)6.7(at)4.3(ed)-295.4(in)-295.8(the)-292.3(7)-1.1(b)-296.8(c)-.8(om)7.2(pl)7.5(eme)4.9(n)1.4(t)4.3(i)1.2(ng)-296.8(ce)4.9(ll)-302.3(l)7.5(i)1.2(ne)]TJ
0 -1.2203 TD
.0145 Tc
[(tha)-4(t)-302.1(e)-4.4(x)-.3(pr)-5.2(ess)-5.8(e)2(s)-309.3(I)-.3(CP4)-307.5(a)-4(nd)-304.6(ICP)-5.8(2)2.3(7)-4(,)-304.6(which)-311.4(i)-1.7(s)-303(d)-1.1(iff)-4.9(e)1.9(r)-5.2(e)2(nt)-308.4(fr)-5.2(om)-305.5(the)]TJ
T*
.0147 Tc
[(cell)-229.1(line)-238.1(used)-234.9(t)1.6(o)-234.7(p).7(r)-5(o)-.7(pagat)-4.7(e)-231.8(t)-4.7(h)-1.3(e)-231.8(N)-4.2(P2)-231.4(v)-5(e)2.2(ctor.)-234.8(A)-239.6(single)-238.1(10-)-4.7(layer)]TJ
0 -1.2266 TD
.0158 Tc
[(cell)-310.2(factory)-311.1(\()2.7(Corning)5.1(,)-315.9(L)6.5(o).4(well,)]TJ
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