公开(公告)号：WO2019134791A1

公开(公告)日：2019-07-11

申请号：PCT/EP2018/084289

申请日：2018-12-11

Applicant: UNIVERSITÄT ZU LÜBECK

Inventor： PETKOVIC, Sonja ,  MÜLLER, Sabine ,  HANSEN, Cathrin ,  SCZAKIEL, Georg

IPC: C12N15/113 ,  C12N15/11

CPC classification number: C12N15/111 ,  C12N2310/113 ,  C12N2310/122 ,  C12N2320/50

Abstract: The present application relates to a method for controlled circularization of RNA comprising the steps of providing an activatable ribozyme structure and performing a ribozyme reaction, to circularized RNA prepared by the method and to an activatable ribozyme structure used in the method.

公开(公告)号：WO2019060779A1

公开(公告)日：2019-03-28

申请号：PCT/US2018/052293

申请日：2018-09-21

Applicant: CITY OF HOPE

Inventor： BURNETT, John, C. ,  EPPS, Elizabeth ,  ROSSI, John, J.

IPC: C07H21/00 ,  C12N7/01 ,  C12N15/11 ,  C12N15/113 ,  C12N15/86 ,  C12N15/867

CPC classification number: C12N15/111 ,  C12N15/1132 ,  C12N15/86 ,  C12N2310/11 ,  C12N2320/33 ,  C12N2330/51 ,  C12N2740/16043 ,  C12N2740/16052 ,  C12N2310/14 ,  C12N2310/531

Abstract: MicroRNAs embedded within an intron, which are called 'mirtrons,' can be used as a platform for expressing one or more shRNA or miRNA mimics in a lentiviral vector. The inventors developed a strategy to improve lentiviral titering by reducing the production of shRNA/miRNA from the vector during packaging through the introduction of splice-inhibiting antisense oligonucleotides during vector packaging, which inhibit the splicing of the mirtron and subsequent processing of the shRNAs/miRNAs. In an aspect is provided a kit comprising an oligonucleotide comprising a mirtron splice site binding sequence and a lentiviral packaging system. In an aspect is provided a method for producing a lentivirus. The method comprises the step of transfecting a cell with an oligonucleotide comprising a mirtron splice site binding sequence and a lentiviral packaging system; thereby producing the lentivirus.

公开(公告)号：WO2019027414A1

公开(公告)日：2019-02-07

申请号：PCT/US2017/044643

申请日：2017-07-31

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： HUN, Jin Hang ,  WEISS, Ron

IPC: C12N15/11 ,  C12Q1/68 ,  C12N15/10

CPC classification number: C12N15/111 ,  C12N15/1086 ,  C12N2320/10

Abstract: Provided herein are genetic circuits and cell state classifiers for detecting the microRNA profile of a cell. The cell state classifiers of the present disclosure are designed to incorporate multiple genetic circuits integrated together by transcriptional or translational control. Multiple inputs can be sensed simultaneously by coupling their detection to different portions of the genetic circuit such that the output molecule is produced only when the correct input profile of miRNAs is detected. The genetic circuits and cell state classifiers may be used in various applications (e.g., therapeutic or diagnostic applications).

公开(公告)号：WO2019023291A2

公开(公告)日：2019-01-31

申请号：PCT/US2018/043588

申请日：2018-07-25

Applicant: DANA-FARBER CANCER INSTITUTE, INC.

Inventor： LIU, Xiaole ,  BROWN, Myles ,  PENG, Jingyu ,  XIAO, Tengfei ,  LI, Wei

CPC classification number: C12N15/111 ,  C12N2310/20 ,  C12N2320/12 ,  C12N2330/31

Abstract: The present disclosure relates to compositions and methods for making and decoding paired-guide RNA (pgRNA) libraries using the Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR) system, and using the resulting pgRNA/CRISPR libraries to identify genetic interactions or functional non-coding elements.

公开(公告)号：WO2018209320A1

公开(公告)日：2018-11-15

申请号：PCT/US2018/032460

申请日：2018-05-11

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE

Inventor： TANG, Weicin ,  HU, Johnny Hao ,  LIU, David, R.

IPC: C12N15/113 ,  C12N15/115 ,  C12N15/11

CPC classification number: C12N15/113 ,  C12N15/111 ,  C12N15/115 ,  C12N2310/12 ,  C12N2310/121 ,  C12N2310/16 ,  C12N2310/20

Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA- programmable proteins, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an "on" or "off" state, which control the binding and, in certain instances, cleavage activity of RNA-programmable proteins (e.g., RNA-programmable endonucleases). By incorporating ligand-responsive self- cleaving catalytic RNAs (aptazymes) into guide RNAs, a set of aptazyme-embedded guide RNAs was developed that enable small molecule-controlled nuclease-mediated genome editing and small molecule-controlled base editing, as well as small molecule-dependent transcriptional activation in mammalian cells.

公开(公告)号：WO2018187519A1

公开(公告)日：2018-10-11

申请号：PCT/US2018/026161

申请日：2018-04-05

Applicant: JIVANA BIOTECHNOLOGY INC. ,  THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS

Inventor： PRABHAKAR, Bellur ,  HOPPS, Sidney ,  MATHUR, Aditi ,  YUE, Fei ,  SAINI, Shikha

IPC: C12N15/113 ,  C12N5/071 ,  A61P31/00 ,  C07H21/02 ,  A61K31/7105

CPC classification number: A61P31/00 ,  A61K31/337 ,  A61K31/7105 ,  A61K45/06 ,  C12N15/111 ,  C12N15/1135 ,  C12N2310/14 ,  C12N2310/531 ,  C12N2320/31 ,  C12N2320/33 ,  A61K2300/00

Abstract: The invention provides compositions and methods for treating cancers comprising administering a combination of antineoplastic agents, wherein the combination comprises taxane derivative chemotherapeutics and one or more nucleic acid molecules capable of down-regulating expression of at least one splice variant of the IG 20 gene, and wherein not ail splice variants of the IG 20 gene are down-regulated. In an embodiment, the splice variant of the IG 20 gene is a MADD splice variant and the nucleic acid molecules are siRNA, shRNA and antisense oligonucleotides which comprise a nucleic acid sequence complementary to a nucleic acid sequence of exon 13L of the MADD splice variant or to an mRNA transcript of exon 13L of the MADD splice variant. The invention encompasses methods of treating cancers which include combination therapy with nucleic acid molecules capable of down-regulating the expression of the at least one splice variant of the IG 20 gene, and taxane derivative chemotherapeutics.

公开(公告)号：WO2018183766A1

公开(公告)日：2018-10-04

申请号：PCT/US2018/025282

申请日：2018-03-29

Applicant: EDITAS MEDICINE, INC.

Inventor： STEINBERG, Barrett Ethan

IPC: C12N15/10 ,  C12N9/22

CPC classification number: C12N15/1058 ,  C12N9/22 ,  C12N15/111 ,  C12N2320/13

Abstract: The present disclosure relates to methods of selection of polynucleotides or polypeptides of interest.

公开(公告)号：WO2018075264A1

公开(公告)日：2018-04-26

申请号：PCT/US2017/055475

申请日：2017-10-06

Applicant: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.

Inventor： LEVY, Matthew ,  BHOWMICK, Arijit

IPC: A61K31/7088 ,  C12N15/10 ,  C12N15/115

CPC classification number: C12N15/115 ,  C12N15/111 ,  C12N2320/51

Abstract: Provided are chemically modified ribonucleic acid (RNA) aptamers comprising one or more of 2'F guanylate, 2'OMe cytidylate, 2'OMe adenylate, and a deoxy pyrimidine nucleotide with a moiety on the 5 position of the pyrimidine; and methods of making the aptamers.

Abstract translation: 提供包含2'F鸟苷酸，2'OMe胞苷酸，2'OMe腺苷酸和脱氧嘧啶核苷酸中的一个或多个的化学修饰的核糖核酸（RNA）适体，其5位上具有部分 的嘧啶; 和制作适配体的方法。

公开(公告)号：WO2018067302A2

公开(公告)日：2018-04-12

申请号：PCT/US2017/052318

申请日：2017-09-19

Applicant: NORTH WESTERN UNIVERSITY

Inventor： MIRKIN, Chad, A. ,  WERTHEIM, Jason A. ,  GUAN, Chenxia Monica ,  COLE, Lisa ,  FERRER, Jennifer Rachel ,  YAMANKURT, Gokay ,  WANG, Shuya

IPC: A61K48/00 ,  A61K47/69

CPC classification number: A61K47/6911 ,  A61K9/0019 ,  A61K9/127 ,  A61K31/18 ,  A61K31/685 ,  A61K31/7105 ,  A61K31/711 ,  A61K31/713 ,  A61K35/13 ,  A61K38/12 ,  A61K39/0011 ,  A61K39/001192 ,  A61K39/39 ,  A61K45/06 ,  A61K2039/55511 ,  A61K2039/55555 ,  A61K2039/55561 ,  A61K2039/55572 ,  A61K2039/812 ,  A61P9/10 ,  A61P35/00 ,  C07K17/04 ,  C12N15/111 ,  C12N15/88 ,  C12N2310/17 ,  C12N2310/3515 ,  C12N2320/32 ,  A61K2300/00

Abstract: The present disclosure relates to liposomal particles, liposomal particles having encapsulated agents, methods of making the same, and uses thereof. Liposomal particles are useful in gene regulation and drug delivery.

Abstract translation: 本公开涉及脂质体颗粒，具有胶囊剂的脂质体颗粒，其制备方法及其用途。 脂质体颗粒可用于基因调控和药物递送。

公开(公告)号：WO2018053795A1

公开(公告)日：2018-03-29

申请号：PCT/CN2016/099849

申请日：2016-09-23

Applicant: SHANGHAI JIAO TONG UNIVERSITY

Inventor： JIN, Tuo ,  CHEN, Shun

IPC: C12N15/64 ,  A61K47/34 ,  A61K48/00 ,  C08G73/04

CPC classification number: C12N15/10 ,  C12N15/111 ,  C12N2310/14 ,  C12N2320/32

Abstract: This invention demonstrated a unique cationic polymer that possesses a number features essential for systemic delivery of nucleic acids simultaneously. First, this polymer was synthesized by Zeta potential-regulated condensation of linear and branched amino group bearing oligomers through imidazole-4, 5-imine linkages, wherein the polymer diameter can be precisely adjusted from tens to hundreds nanometers by Zeta potential determinates such NaCl concentration. Most interestingly, the polymer was structured with sufficient network cavity to pack plenty copies of siRNA intramolecularly to form a polyplex of single polymer molecule. In addition, the polymer backbone degraded readily to non-toxic species and released nucleic acids in response to cellular environment due to the pKa (5.9) of its aromatically conjugated imine linage. Finally, the polyplex of single polymer molecule can be further encapsulated by a self-assembled a unilamella membrane of rationally designed triblock copolymer to which selected functional components such as cell targeting agents can be immobilized in optimized population. The lack of medicinally feasible synthetic carriers remains as the standing-hurdle blocking nucleic acids to covert from therapeutic actives to practical medicines. The present invention may serve as a "universal" vehicle to equip with variety of delivery functions for its defined structure and compatible flexibility.

Abstract translation: 本发明展示了一种独特的阳离子聚合物，其具有对于同时全身递送核酸必不可少的数个特征。 首先，该聚合物通过咪唑-4,5-亚胺键的直链和支链氨基基团低聚物的Zeta电位调节缩合合成，其中聚合物直径可以通过Zeta电位确定如NaCl浓度从数十至数百纳米精确调节 。 最有趣的是，聚合物结构具有足够的网络空腔以分子内包装大量siRNA以形成单聚合物分子的多聚体。 另外，由于其芳香族共轭亚胺谱系的pKa（5.9），聚合物骨架容易降解成无毒物质并释放核酸以响应细胞环境。 最后，单聚合物分子的多聚体可以通过自组装的合理设计的三嵌段共聚物的单层膜进一步包封，选择的功能组分如细胞靶向剂可以固定在优化的群体中。 医学上可行的合成载体的缺乏仍然是阻止核酸从治疗活性成分转化为实际药物的常规障碍。 本发明可以用作“通用” 车辆配置各种交付功能的定义结构和兼容的灵活性。