Nucleic acid molecules and uses thereof

Abstract

The present disclosure provides nucleic acid molecules comprising a first inverted terminal repeat (ITR), a second ITR, and a genetic cassette encoding a miRNA and / or a therapeutic protein. In certainembodiments, the therapeutic protein comprises a clotting factor, e.g., a FVIII polypeptide, a FIX polypeptide, or a fragment thereof. In some embodiments, the first ITR and / or the second ITR is an ITR of a non-adeno-associated virus (AAV). The present disclosure also provides methods of treating bleeding disorders such as hemophilia comprising administering to the subject the nucleic acid molecule or a polypeptide encoded thereby.

Description

[0001] References to Sequence Listings Submitted Electronically [0002] The contents of the Sequence Listing (name: 4159_493PC01_ST25; size: 434,561 bytes; and date of creation: August 9, 2018) as electronically filed as an ASCII text file are incorporated herein by reference in their entirety. [0003] Background of the Invention [0004] Gene therapy offers a durable treatment for many diseases. In the past, gene therapy has often relied on the use of viruses. A number of viral agents can be selected for this purpose, each with unique properties that will make them more or less suitable for gene therapy. Zhou et al, Adv Drug Deliv Rev. 106(Pt A): 3-26, 2016. However, the undesired properties of some viral vectors, including their immunogenicity or propensity to cause cancer, have led to clinical safety concerns, and until recently, their current clinical use was limited to certain applications, such as vaccines and oncolysis Strategy. Cotter et al, Front Biosci. 10:1098-...

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Problems solved by technology

Furthermore, anti-AAV neutralizing antibodies induced by AAV treatment hamper repeated AAV treatment when the first AAV treatment fails to achieve therapeutic efficacy levels

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