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Well-documented cases exist, but the term is often applied to whatever a nonspecific precipitation step removes, and some studies use methods that cannot actually confirm what was present

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For example, dosages of 1,000 mcg or more are routinely used to treat deficiencies without major concern for toxicity

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Possible explanations include unacceptable toxicity in human subjects, business strategy changes at Arrowhead Research Corporation (which shifted focus to RNA therapeutics), regulatory challenges, or a combination of factors

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