Carnegie Mellon University

Yale University

University of Connecticut

Raman Bahal

Danith H Ly

Arunava Manna

Yidan Cong

Dinesh Chandra Bhunia

W Mark Saltzman

Wei-Che Hsieh

Peter M Glazer

Naftali Kaminski

Srinivas Rapireddy

Elias Quijano

Armin Tahmasbi Rad

Mu-Ping Nieh

Farida Ahangari

Nicole Ali McNeer

Carlos Fernandez-Hernando

Rapireddy Srinivas

Shipra Malik

In one aspect, the present disclosure provides a microRNA-33 (miR-33) inhibitor comprising a peptide nucleic acid covalently bound to a pH low insertion peptide. In another aspect, the present disclosure provides a method of treating pulmonary fibrosis in a subject, the method comprising administering to the subject a therapeutically effective amount of the miR-33 inhibitor. In some embodiments, the pulmonary fibrosis is idiopathic pulmonary fibrosis.

MicroRNA-33 inhibitors and use thereof in the treatment of pulmonary fibrosis

Described herein are genetic recognition reagents comprising terminal aromatic moieties that bind specifically to a template nucleic acid and concatenate. Also provided are methods of using the genetic recognition reagents, e.g., to treat or diagnose a repeat expansion disorder, such as DMI.

Template-directed nucleic acid targeting compounds

A self-assembled discoidal PNA delivery vehicle includes a zwitterionic short chain diacyl lipid, a zwitterionic long chain diacyl lipid, a charged long chain diacyl lipid, a PEGylated lipid of the formula distearoyl phosphoethanolamine (DSPE)-PEG-TG, and an encapsulated PNA molecule with a defined molar ratio of the zwitterionic long chain diacyl lipid and the charged long chain diacyl lipid to the short chain diacyl lipid, the molar ratio of the charged long chain diacyl lipid to the zwitterionic long chain diacyl lipid, molar % of the PEGylated lipid to all lipids, and ratio of PNA to lipid. Also described are method of self-assembling the discoidal PNA delivery vehicle and methods of enhancing cellular uptake of PNA using the discoidal PNA delivery vehicle.

Discoidal nano universal platform for efficient delivery of PNAs

Described herein are recognition modules that bind specifically to a template nucleic acid and which ligate together in a reducing environment to produce a gamma peptide nucleic acid (&#x3b3;PNA) oligomer. Also provided are methods of synthesizing a &#x3b3;PNA oligomer on a template using the recognition modules.

Template-directed PNA synthesis process and PNA targeting compounds

Compositions and methods for enhancing targeted gene editing and methods of use thereof are disclosed. In the most preferred embodiments, gene editing is carried out utilizing a gene editing composition such as triplex-forming oligonucleotides, CRISPR, zinc finger nucleases, TALENS, or others, in combination with a gene modification potentiating agent such as stem cell factor (SCF), a CHK1 or ATR inhibitor, or a combination thereof. A particular preferred gene editing composition is triplex-forming peptide nucleic acids (PNAs) substituted at the &#x3b3; position for increased DNA binding affinity. Nanoparticle compositions for intracellular delivery of the gene editing composition are also provided and particular advantageous for use with in vivo applications.

Compositions for enhancing targeted gene editing and methods of use thereof

Template-directed &#x3b3;PNA synthesis process and &#x3b3;PNA targeting compounds

Growing community of inventors

Hamden, CT, United States of America

Raman Bahal