iPSC-Derived Platelet Drug Delivery for Protein Therapeutic Loading
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Solution Overview
Problem
Current methods for producing platelets are inefficient, leading to shortages and variability in donor-derived platelets, and existing nanoparticle-based drug delivery systems are ineffective for protein-based therapeutics due to size limitations and immune responses.
Innovation Solution
Developing compositions and methods to produce induced pluripotent stem cell (iPSC)-derived megakaryocytic progenitors, megakaryocytes, proplatelets, and platelets, which can be loaded with therapeutic agents through receptor-mediated, passive, or covalent conjugation, and genetically engineered to enhance drug delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If nanoparticle-based approaches are used for drug delivery, then tissue-targeted delivery of small molecules is improved, but protein-based therapeutics cannot be packaged due to size limitations
Solution Approach 1:
The patent changes the size parameter of the delivery vehicle from nanoparticle scale to microparticle scale (platelets are 2-10 µm), enabling packaging of protein-based therapeutics while maintaining targeted delivery capabilities through physiological processes
2Reliability
If nanoparticle-based approaches are used for drug delivery, then tissue-targeted delivery is enhanced, but less than 1% of injected nanoparticles accumulate in targeted sites
Solution Approach 1:
The patent leverages the platelet's natural physiological function of homeostatic accumulation at sites of vascular injury or cancer, allowing the delivery vehicle to autonomously target diseased tissue without requiring complex external targeting mechanisms
Solution Approach 2:
The platelet delivery vehicle serves multiple functions: it acts as both a therapeutic agent (through its physiological functions) and a drug carrier, while naturally accumulating at target sites through its inherent biological properties rather than engineered targeting moieties
3Productivity
If PEG components are used in nano-formulations, then drug delivery is achieved, but adverse immune responses compromise efficacy upon repeated injections
Solution Approach 1:
The patent uses platelets that can be derived from patient-specific iPSCs, providing a renewable, non-immunogenic source of delivery vehicles that can be administered repeatedly without triggering immune responses against formulation components
4Ease of operation
If donor-derived platelets are used, then platelet transfusion is provided, but shortages and wide functional variability limit effectiveness
Solution Approach 1:
The patent creates copies of functional platelets through differentiation of patient-specific iPSCs into megakaryocytes and subsequent platelet production, providing unlimited supply of consistent, functional platelets without relying on donor variability
Solution Approach 2:
The patent performs preliminary genetic engineering of iPSCs to incorporate therapeutic genes before differentiation, ensuring that the resulting platelets are pre-loaded with therapeutic capabilities and will function consistently upon administration
Data Source
AI summary
Methods for producing megakaryocytes and platelets derived from inducible pluripotent stem cells are provided. Such megakaryocytes or platelets can be genetically modified to comprise a nucleic acid molecule encoding a therapeutic agent. The present disclosure further provides methods and compositions for loading a platelet or a megakaryocyte with a therapeutic agent and for genetically modifying a platelet or a megakaryocyte to express an agent.