A
Akin Akinc
Researcher at Alnylam Pharmaceuticals
Publications - 121
Citations - 15926
Akin Akinc is an academic researcher from Alnylam Pharmaceuticals. The author has contributed to research in topics: Small interfering RNA & Gene silencing. The author has an hindex of 43, co-authored 120 publications receiving 13519 citations. Previous affiliations of Akin Akinc include Massachusetts Institute of Technology.
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Journal ArticleDOI
Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs
Jürgen Soutschek,Akin Akinc,Birgit Bramlage,Klaus Charisse,Rainer Constien,Mary Donoghue,Sayda Elbashir,Anke Geick,Philipp Hadwiger,Jens Harborth,Matthias John,Venkitasamy Kesavan,Gary Lavine,Rajendra K. Pandey,Timothy Racie,Kallanthottathil G. Rajeev,Ingo Röhl,Ivanka Toudjarska,Gang Wang,Silvio Wuschko,David Bumcrot,Victor Koteliansky,Stefan Limmer,Muthiah Manoharan,Hans-Peter Vornlocher +24 more
TL;DR: In this article, chemically modified short interfering RNAs (siRNAs) were used to silence an endogenous gene encoding apolipoprotein B (apoB) after intravenous injection in mice.
Journal ArticleDOI
Rational design of cationic lipids for siRNA delivery
Sean C. Semple,Akin Akinc,Jianxin Chen,Ammen P. Sandhu,Barbara L. Mui,Connie K Cho,Dinah W.Y. Sah,Derrick Stebbing,Erin J Crosley,Ed Yaworski,Ismail M. Hafez,J. Robert Dorkin,June Qin,Kieu Lam,Kallanthottathil G. Rajeev,Kim F. Wong,Lloyd Jeffs,Lubomir Nechev,Merete L. Eisenhardt,Muthusamy Jayaraman,Mikameh Kazem,Martin Maier,Masuna Srinivasulu,Michael J Weinstein,Qingmin Chen,Rene Alvarez,Scott A Barros,Soma De,Sandra K. Klimuk,Todd Borland,Verbena Kosovrasti,William Cantley,Ying K. Tam,Muthiah Manoharan,Marco A. Ciufolini,Mark A Tracy,Antonin de Fougerolles,Ian MacLachlan,Pieter R. Cullis,Thomas D. Madden,Michael J. Hope +40 more
TL;DR: The best-performing lipid recovered after screening (DLin-KC2-DMA) was formulated and characterized in SNALP and demonstrated to have in vivo activity at siRNA doses as low as 0.01 mg/kg in rodents and 0.1 mg/ kg in nonhuman primates, a substantial improvement over previous reports of in vivo endogenous hepatic gene silencing.
Journal ArticleDOI
RNAi-mediated gene silencing in non-human primates
Tracy Zimmermann,Amy C.H. Lee,Akin Akinc,Birgit Bramlage,David Bumcrot,Matthew N. Fedoruk,Jens Harborth,James Heyes,Lloyd Jeffs,Matthias John,Adam Judge,Kieu Lam,Kevin McClintock,Lubomir Nechev,Lorne R. Palmer,Timothy Racie,Ingo Röhl,Stephan Seiffert,Sumi Shanmugam,Vandana Sood,Jürgen Soutschek,Ivanka Toudjarska,Amanda J. Wheat,Ed Yaworski,William Zedalis,Victor Koteliansky,Muthiah Manoharan,Hans-Peter Vornlocher,Ian MacLachlan +28 more
TL;DR: It is shown that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B in non-human primates, supporting RNAi therapeutics as a potential new class of drugs.
Journal ArticleDOI
Image-based analysis of lipid nanoparticle–mediated siRNA delivery, intracellular trafficking and endosomal escape
Jerome Gilleron,William Querbes,Anja Zeigerer,Anna Borodovsky,Giovanni Marsico,Undine Schubert,Kevin Manygoats,Sarah Seifert,Cordula Andree,Martin Stöter,Hila Epstein-Barash,Ligang Zhang,Victor Koteliansky,Kevin Fitzgerald,Eugenio Fava,Marc Bickle,Yannis Kalaidzidis,Akin Akinc,Martin Maier,Marino Zerial +19 more
TL;DR: It is estimated that escape of siRNAs from endosomes into the cytosol occurs at low efficiency (1–2%) and only during a limited window of time when the LNPs reside in a specific compartment sharing early and late endosomal characteristics.
Journal ArticleDOI
Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms.
Akin Akinc,William Querbes,Soma De,June Qin,Maria Frank-Kamenetsky,K. Narayanannair Jayaprakash,Muthusamy Jayaraman,Kallanthottathil G. Rajeev,William Cantley,J. Robert Dorkin,James Butler,Liuliang Qin,Timothy Racie,Andrew Sprague,Eugenio Fava,Anja Zeigerer,Michael J. Hope,Marino Zerial,Dinah W.Y. Sah,Kevin Fitzgerald,Mark A Tracy,Muthiah Manoharan,Victor Koteliansky,Antonin de Fougerolles,Martin Maier +24 more
TL;DR: A targeting approach using an exogenous ligand containing a multivalent N-acetylgalactosamine (GalNAc)-cluster, which binds with high affinity to the asialoglycoprotein receptor (ASGPR) expressed on hepatocytes appears to be highly effective for the delivery of iLNPs to liver.