Exploiting the diphtheria toxin internalization receptor enhances delivery of proteins to lysosomes for enzyme replacement therapy.
Exploiting the diphtheria toxin internalization receptor enhances delivery of proteins to lysosomes for enzyme replacement therapy.
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DOI：
10.1126/sciadv.abb0385
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发表时间：
2020-12
期刊：
影响因子：
13.6
通讯作者：
Melnyk RA
中科院分区：
文献类型：
--
作者：
Sugiman-Marangos SN;Beilhartz GL;Zhao X;Zhou D;Hua R;Kim PK;Rini JM;Minassian BA;Melnyk RA
Engineering lysosomal enzymes to bind the diphtheria toxin receptor with high affinity increases uptake into cells and tissues. Enzyme replacement therapy, in which a functional copy of an enzyme is injected either systemically or directly into the brain of affected individuals, has proven to be an effective strategy for treating certain lysosomal storage diseases. The inefficient uptake of recombinant enzymes via the mannose-6-phosphate receptor, however, prohibits the broad utility of replacement therapy. Here, to improve the efficiency and efficacy of lysosomal enzyme uptake, we exploited the strategy used by diphtheria toxin to enter into the endolysosomal network of cells by creating a chimera between the receptor-binding fragment of diphtheria toxin and the lysosomal hydrolase TPP1. We show that chimeric TPP1 binds with high affinity to target cells and is efficiently delivered into lysosomes. Further, we show superior uptake of chimeric TPP1 over TPP1 alone in brain tissue following intracerebroventricular injection in mice lacking TPP1, demonstrating the potential of this strategy for enhancing lysosomal storage disease therapy.
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DOI：
10.1074/jbc.m112.438663
发表时间：
2013-01-18
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Maga JA;Zhou J;Kambampati R;Peng S;Wang X;Bohnsack RN;Thomm A;Golata S;Tom P;Dahms NM;Byrne BJ;LeBowitz JH
通讯作者：
LeBowitz JH
影响因子：
2.8
作者：
Klinge, L;Straub, V;Voit, T
通讯作者：
Voit, T
DOI：
10.1073/pnas.1218620110
发表时间：
2013-03-26
影响因子：
11.1
作者：
Li, Zhijie;Michael, Iacovos P.;Rini, James M.
通讯作者：
Rini, James M.
影响因子：
3.1
作者：
MORRIS, RE;GERSTEIN, AS;SAELINGER, CB
通讯作者：
SAELINGER, CB
DOI：
10.1016/j.omtm.2017.03.006
发表时间：
2017-06-16
期刊：
Molecular therapy. Methods & clinical development
影响因子：
--
作者：
Liu L;Lee WS;Doray B;Kornfeld S
通讯作者：
Kornfeld S