Polynucleotide sequence for the inhibition of phospholamban synthesis

Simple SummaryContent extracted from patent full text and abstract with AI.

This patent describes a genetic approach to treating heart conditions by using specially designed DNA or RNA sequences to inhibit the synthesis of phospholamban, a key protein regulating calcium cycling in heart muscle cells. The invention provides sequences that, when introduced into heart cells, are transcribed into RNA that forms a hairpin structure, which the cell processes into siRNA. This siRNA specifically degrades phospholamban mRNA, reducing the protein's production. Promoters that are either drug-inducible or heart cell-specific control the expression of these sequences, ensuring selective or controllable action.

Use CasesContent extracted from patent full text and abstract with AI.

• Gene therapy for treating heart failure or cardiomyopathy by improving cardiac muscle contractility.
• Development of viral or non-viral delivery systems for cardiac-specific gene silencing therapies.
• Research tool for studying the role of phospholamban in cardiac physiology and disease.
• Potential veterinary applications for treating heart conditions in animals (e.g., dogs, horses).
• Combination therapies with increased SERCA expression for synergistic improvement of heart function.

BenefitsContent extracted from patent full text and abstract with AI.

• Provides a targeted approach to decrease phospholamban levels, thereby potentially enhancing heart function in patients with heart failure.
• Utilizes stable DNA delivery rather than unstable RNA, improving practicality for drug development and gene therapy.
• Reduces off-target effects and increases safety by employing cardiac-specific or drug-inducible promoters.
• Enables regulated or tissue-specific intervention, limiting unwanted systemic effects.
• May be delivered via several platforms (viral vectors, naked DNA, liposomes), increasing flexibility and adaptability for clinical and research applications.

Technical Classifications (CPCs)

Inventors & Applicants

Patent Abstract

A DNA polynucleotide sequence is disclosed that comprises a transcribed sequence, and a promoter sequence. Transcription of the transcribed sequence by an RNA polymerase in a cell renders an RNA a transcript capable of forming a partially self-complementary hairpin structure which can be processed by the cell to an siRNA product that can degrade phospholamban mRNA in such cell. The promoter is a drug inducible conditional promoter or a cardiomyocyte cell-specific promoter or both, operably linked to the transcribed sequence. The promoter is operable by an RNA polymerase naturally occurring in a mammalian cell.