I
Ian MacLachlan
Researcher at United States Army Medical Research and Materiel Command
Publications - 79
Citations - 12746
Ian MacLachlan is an academic researcher from United States Army Medical Research and Materiel Command. The author has contributed to research in topics: Small interfering RNA & Gene silencing. The author has an hindex of 38, co-authored 79 publications receiving 11964 citations.
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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
Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs
David Morrissey,Jennifer A. Lockridge,Lucinda Shaw,Karin Blanchard,Kristi Jensen,Wendy Breen,Kimberly Hartsough,Lynn Machemer,Susan Radka,Vasant Jadhav,Narendra K. Vaish,Shawn Zinnen,Chandra Vargeese,Keith Bowman,Chris S. Shaffer,Lloyd Jeffs,Adam Judge,Ian MacLachlan,Barry Polisky +18 more
TL;DR: The advances demonstrated here, including persistence of in vivo activity, use of lower doses and reduced dosing frequency are important steps in making siRNA a clinically viable therapeutic approach.
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Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA.
TL;DR: It is reported that synthetic siRNAs formulated in nonviral delivery vehicles can be potent inducers of interferons and inflammatory cytokines both in vivo in mice and in vitro in human blood.
Journal ArticleDOI
Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo
TL;DR: It is shown that immune stimulation by synthetic siRNA can be completely abrogated by selective incorporation of 2'-O-methyl (2'OMe) uridine or guanosine nucleosides into one strand of the siRNA duplex, enabling therapeutically viable siRNA doses without cytokine induction, toxicity, or off-target effects associated with the use of unmodified siRNA.