Antisense Oligonucleotides Target Bcl-6 mRNA for Lymphoma Apoptosis
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Solution Overview
Problem
BCL-6 protein is frequently deregulated in non-Hodgkin lymphomas, leading to over-expression due to 3q27 translocations, which results in abnormal cell growth and tumor formation, and existing methods are inadequate in effectively targeting this deregulation for cancer treatment.
Innovation Solution
Administration of nucleic acid molecules complementary or corresponding to the bcl-6 mRNA, such as antisense oligonucleotides or short interfering RNA, to reduce bcl-6 protein levels, inducing apoptosis in bcl-6-expressing cells, thereby treating cancers with bcl-6-expressing cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing methods are used to treat lymphoma, then general cancer treatment approaches are applied, but they are inadequate in effectively targeting bcl-6 deregulation
Solution Approach 1:
The patent segments the treatment approach by specifically targeting the bcl-6 gene and its mRNA transcript, rather than applying general cancer treatment methods. This is achieved through antisense oligonucleotides that specifically bind to bcl-6 mRNA sequences, dividing the treatment strategy into a targeted molecular approach that addresses the specific deregulation mechanism in non-Hodgkin lymphomas
Solution Approach 2:
The patent introduces antisense oligonucleotides as intermediary molecules that mediate between the treatment goal and the target. These oligonucleotides serve as intermediaries that specifically bind to bcl-6 mRNA, preventing its translation into protein and thereby indirectly achieving cancer cell death through targeted gene silencing rather than direct cytotoxic action
2Reliability
If bcl-6 protein levels are reduced using nucleic acid molecules, then apoptosis is induced in bcl-6-expressing cells, but this requires specific targeting of mRNA sequences
Solution Approach 1:
The patent applies local quality by designing antisense oligonucleotides that target specific local regions of the bcl-6 mRNA sequence. Rather than attempting to affect the entire mRNA molecule, the invention focuses on binding to particular accessible sequences within the bcl-6 transcript, achieving precise local interaction that triggers downstream apoptotic effects
Solution Approach 2:
The patent replaces mechanical or chemical cytotoxic mechanisms with a molecular recognition system. Instead of using drugs that physically damage cells or disrupt general cellular functions, the invention employs nucleic acid-based molecular recognition where antisense oligonucleotides specifically hybridize to complementary bcl-6 mRNA sequences, substituting non-specific mechanical action with precise molecular binding
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The approach effectively decreases bcl-6 mRNA and protein levels, reducing lymphoma cell viability and inducing apoptosis, providing a targeted method for treating bcl-6-expressing cancer cells.
Implementation Method 1
a composition comprising a nucleic acid molecule complementary to or corresponding to a region of the mRNA molecule
Data Source
AI summary
This invention provides methods of inducing apoptosis in a bcl-6-expressing cell and methods of treating a subject with a cancer comprising a bcl-6-expressing cell, comprising administration of a composition that reduces the amount of the bcl-6 protein or of an mRNA molecule encoding same, a composition comprising a nucleic acid molecule complementary to or corresponding to a region of the mRNA molecule, or a vector expressing the nucleic acid molecule. In another embodiment, the present invention provides an isolated nucleic acid molecule having a sequence corresponding to or complementary to accessible regions of bcl-6 mRNA, and vectors, cells, compositions, and kits comprising same.